1.Effects of decoction of Euphorbia fischeriana Steud.and jujuba against breast cancer of different molecular phenotypes via PI3k/Akt pathway
Liwei MA ; Hongyu YAO ; Zhe CHEN ; Shiyu NI ; Song CHEN ; Jing LI ; Jicheng LIU
Chinese Journal of Comparative Medicine 2024;34(3):27-35
Objective To explore the effect of decoction of Euphorbia fischeriana Steud.and jujuba(DEFSJ)against estrogen receptor(ER)negative(-)and ER positive(+)breast cancer via the PI3k/Akt pathway,and to provide a reference for the targeted treatment of breast cancer.Methods DEFSJ extract was prepared and analyzed using UHPLC-Triple Quad.DEFSJ containing serum(CS)was prepared via a serum pharmacology method.Different concentrations of DEFSJ-CS were applied to(ER-)MDA-MB-453 and(ER+)MCF-7 breast cancer cells in vitro for 48 h.The distribution of cells in different stages of the cellular cycle was evaluated using a Flow cytometer.DNA ladder assay was used to assess the degree of apoptosis,and the expression of PI3k/Akt pathway-related proteins was evaluated by Western blot assay.The expression of FoxO3a,FoxOla,and Bim mRNA was detected by Real-time quantitative PCR.Nuclear transposition of FoxO3a protein was analysed using a confocal laser microscopy.Results Five batches of DEFSJ extract were analyzed using UPLC,and the result showed that the preparation technology was feasible and the quality was controllable,ensuring the accuracy of the pharmacological experiment result.DEFSJ-CS blocked cells in the G2/M phase(P<0.05,P<0.01).Cells treated with DEFSJ-CS displayed the typical apoptotic ladder in the DNA ladder experiment.Compared with the negative control cells,the DEFSJ-CS group cells had decreased protein expression of p-PI3k,p-Akt,p-FoxO3a,and p-FoxO1a(P<0.05,P<0.01);increased protein expression of Bim(P<0.05);decreased mRNA expression of FoxO3a and FoxO1a(P<0.05,P<0.01);increased mRNA expression of Bim(P<0.05,P<0.01);and enhanced nuclear translocation of FoxO3a protein.The data showed that DEFSJ-CS had a stronger effect on(ER-)MDA-MB-453 cells than(ER+)MCF-7 cells.Conclusions The regulatory effect of DEFSJ extract on anti-breast cancer involves the PI3k/Akt pathway,and the effect varies with phenotypic differences.
2.Thulium laser enucleation versus plasma kinetic resection of the prostate in the treatment of benign prostatic hyperplasia
Wei-Dong ZHANG ; Wen-Jia WANG ; Zhi-Qiang SONG ; Zhe MA ; Jia-Wei ZHANG ; Hao-Hao WANG ; Jian-Chen WU
National Journal of Andrology 2024;30(6):514-518
Objective:To compare thulium laser enucleation of the prostate(ThuLEP)with plasma kinetic resection of the prostate(PKRP)in the treatment of BPH.Methods:We retrospectively analyzed the medical records of 160 cases of BPH treated by ThuLEP(the observation group,n=80)or PKRP(the control group,n=80)in our hospital from January 2021 to December 2023.We recorded the operation time,bladder irrigation time,catheter retention time,hospitalization time,postoperative complica-tions,and pre-and postoperative maximum urinary flow rate(Qmax),residual urine volume(PVR),prostate-specific antigen(PSA)and prostate volume,followed by comparison of the data obtained between the two groups of patients.Results:Compared with the controls,the patients of the observation group showed significantly shorter operation time([67.25±7.24]vs[60.10±5.15]min,P<0.05),bladder irrigation time([46.90±10.77]vs[43.24±6.65]h,P<0.05),catheterization time([5.60±1.31]vs[5.03±1.24]d,P<0.05)and hospitalization time([7.31±2.00]vs[6.55±1.67]d,P<0.05),higher Qmax([18.50±1.24]vs[20.68±1.45]ml/s,P<0.05),lower PVR([12.10±3.53]vs[10.82±3.10]ml,P<0.05),PSA([4.60±0.78]vs[3.38±0.40]μg/L,P<0.05)and prostate volume([25.35±6.46]vs[20.12±5.13]ml,P<0.05)at 3 months after surgery,but no statistically significant difference in the total incidence of postoperative complications(7.50%[6/80]vs 5.00%[4/80],P>0.05).Conclusion:ThuLEP,with its advantages of notable effect,short operation and hospitaliza-tion time,significant improvement of urinary flow dynamics and prostate function,deserves clinical promotion for the treatment of BPH.
3.Circ-0007766 acts as a miR-1972 sponge to promote breast cancer cell migration and invasion via upregulation of HER2
Junxiu ZHAO ; Yi ZHU ; Xiaoyu SONG ; Chao ZHE ; Yuhan XIAO ; Yunduo LIU ; Linhai LI ; Bin XIAO
China Oncology 2024;34(10):915-930
Background and purpose:Human epidermal growth factor receptor 2(HER2)serves as one of the paramount drivers of breast cancer metastasis,with roughly 20%-30%of breast cancer patients exhibiting high expression of HER2.The expression level of HER2 is regulatable at multiple molecular levels and determines the metastatic potential of breast cancer cells;however,the manner in which HER2 expression is modulated at the mRNA level remains ambiguous.Circ-0007766 is a circRNA originated from the coding gene ERBB2 for HER2,and whether circ-0007766 can regulate HER2 expression via the ceRNA mechanism has not been reported.This study aimed to analyze whether circ-0007766 acts as a miR-1972 sponge to promote breast cancer cell migration and invasion via upregulation of HER2 expression.Methods:In this study,a high-throughput circRNA chip was employed to screen for circRNAs that exhibited highly specific expression in HER2-positive breast cancer cells.RNA fluorescence in situ hybridization(FISH)was utilized to detect the subcellular localization of circ-0007766.The BaseScope experiment was conducted to analyze the expression level of circ-0007766 in breast cancer tissues and its clinical diagnostic significance.Breast cancer cell models with overexpression and knockdown of circ-0007766 were constructed by transfecting cloning plasmids and siRNA in vitro.The effect of circ-0007766 on the migration and invasion of breast cancer cells was assessed using transwell migration and invasion experiments,and the migration and invasion abilities of MDA-MB-231 and SK-BR-3 cells were measured.Additionally,it was evaluated whether circ-0007766 could promote the migration and invasion of breast cancer cells through miR-1972.A dual luciferase reporter gene assay was used to verify whether circ-0007766 could regulate HER2 expression by binding to miR-1972.The direct interaction between circ-0007766 and miR-1972 was further verified through the RAP experiment.RIP detection was performed in MDA-MB-231 cells,and the relative 3'UTR of HER2 mRNA was measured by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR).Western blot was used to detect the protein expressions.Results:Circ-0007766 was conspicuously highly expressed in HER2-positive breast cancer cells and distributed in both the cytoplasm and nucleus of cells,with the preponderance being in the cytoplasm.The expression level of circ-0007766 was strikingly higher in breast cancer tissues than in para-cancerous tissues.The expression of circ-0007766 was significantly elevated in HER2-positive breast cancer samples compared with HER2-negative samples.The overexpression(knockdown)of circ-0007766 in HER2-negative breast cancer cells(in HER2-positive breast cancer cells)was capable of promoting(inhibiting)the migration and invasion of breast cancer cells.Circ-0007766 directly bound to miR-1972,which inhibited breast cancer cell migration and invasion,thereby forming an endogenous competitive RNA(ceRNA)regulatory network and impeding the downregulation of HER2 mRNA and protein expression mediated by miR-1972.Circ-0007766 could potentiate the inhibitory effect of miR-1972 on HER2-mediated breast cancer cell migration and invasion that was negatively regulated by miR-1972.CircRNAs sequestered miRNAs to function as ceRNAs,thereby regulating gene expression at both the transcriptional and translational levels.Finally,we discovered that the expressions of circ-0007766 and HER2 were positively correlated in breast cancer cell and tissue samples,while the expression levels of miR-1972 and HER2 were negatively correlated.Circ-0007766 could specifically target miR-1972 to hinder its regulatory effect on HER2 expression.Conclusion:This study discovers that circ-0007766 facilitates the migration and invasion of breast cancer cells via the miR-1972/HER2 signal axis,offering a novel biomarker and potential therapeutic target for patients with metastatic HER2-positive breast cancer.
4.Screw placement assisted by robotic navigation in cannulated screw fixation for fracture of scapular coracoid process
Chen WANG ; Hu PAN ; Chen FEI ; Wuqiang JIANG ; Lei LEI ; Fan XU ; Aiming YE ; Zhan WANG ; Kun ZHANG ; Zhe SONG ; Wei FAN
Chinese Journal of Orthopaedic Trauma 2024;26(9):804-809
Objective:To evaluate the screw placement assisted by robotic navigation in cannulated screw fixation for treatment of fracture of scapular coracoid process.Methods:A retrospective study was conducted to analyze the data of 24 patients with fracture of scapular coracoid process who had been treated by cannulated screw fixation at Department of Orthopaedics and Trauma, Red Cross Hospital Affiliated to Xi'an Jiaotong University from January 2020 to December 2023. According to whether the intraoperative screw placement was assisted by robotic navigation or not, the patients were divided into 2 groups. In group A of 11 cases, there were 6 males and 5 females with an age of (47.4±3.4) years whose screw placement was assisted by robotic navigation during the internal fixation with cannulated screws. In group B of 13 cases, there were 10 males and 3 females with an age of (43.5±4.9) years whose screw placement was assisted by conventional C-arm X-ray fluoroscopy during the internal fixation with cannulated screws. The operative time, intraoperative blood loss, fracture healing time, intraoperative fluoroscopy frequency, intraoperative adjustments of guide wire, Constant-Murley score of shoulder function at the last follow-up and postoperative complications were compared between the 2 groups.Results:There was no significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). The follow-up time was (25.3±9.1) months for group A and (27.6±10.8) months for group B, showing no statistically significant difference ( P>0.05). The intraoperative blood loss [(51.8±35.7) mL], intraoperative fluoroscopy frequency [(5.7±1.0) times] and intraoperative adjustments of guide wire [(1.6±0.7) times] in group A were significantly less than those in group B [(123.8±73.9) mL, (12.5±2.7) times, and (5.3±1.0) times] ( P<0.05). There were no significant differences in operative time [(88.2±21.3) min versus (80.4±31.1) min], fracture healing time [(10.0±1.3) weeks versus (11.5±2.7) weeks] or Constant Murley score of shoulder function at the last follow-up [(86.7±6.1) points versus (91.1±10.0) points] between group A and group B ( P>0.05). No patient reported such complications as wound infection, fracture nonunion, or failure of internal fixation during the follow-up period. Conclusions:In the treatment of fracture of scapular coracoid process by cannulated screw fixation, robotic navigation can be used to assist screw placemen to achieve good efficacy comparable to conventional C-arm X-ray fluoroscopy. Moreover, assistance by robotic navigation can help reduce intraoperative blood loss and radiation, and improve surgical accuracy.
5.Zhenwutang Ameliorates Diabetic Kidney Disease in Mice with Spleen-kidney Yang Deficiency via Nrf2/HO-1/GPX4 Signaling Pathway
Zhe ZHAO ; Guangshun CHEN ; Min BAI ; Yuqiu JIN ; Mengyuan TIAN ; Bing SONG ; Zhenhua LIU ; Yanying ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):29-37
ObjectiveTo investigate the effect and mechanism of Zhenwutang on renal oxidative damage in the mouse model of diabetic kidney disease with the syndrome of spleen-kidney Yang deficiency via the nuclear factor erythroid 2-related factor-2 (Nrf2)/heme oxygenase-1 (HO-1)/glutathione peroxidase 4 (GPX4) signaling pathway. MethodTwenty-five 7-week-old SPF-grade male db/m mice and 95 7-week-old SPF-grade male db/db mice were adaptively fed for a week. A blank group was set with the db/m mice without treatment, and the other mice were administrated with Rhei Radix et Rhizoma decoction and hydrocortisone for the modeling of diabetic kidney disease with the syndrome of spleen-kidney Yang deficiency. The modeled mice were randomized into the model, irbesartan (25 mg·kg-1), and high-, medium-, low-dose (33.8, 16.9, 8.45 g·kg-1) Zhenwutang groups (n=15) and administrated with corresponding drugs for 8 weeks. The survival status of mice was observed, and the traditional Chinese medicine (TCM) syndrome score was recorded. The indicators related to spleen-kidney Yang deficiency, fasting blood glucose (FBG), and renal function indicators were determined. Hematoxylin-eosin staining was employed to observe the histopathological changes of the renal tissue in each group. Biochemical kits were used to determine the oxidative stress-related indicators in the renal tissue. Real-time polymerase chain reaction and Western blotting were employed to determine the mRNA and protein levels, respectively, of Nrf2, HO-1, glutamate-cysteine ligase catalytic subunit (GCLC), and GPX4 in the renal tissue of mice in each group. ResultCompared with the blank group, the modeling increased the TCM syndrome score (P<0.05), elevated the estradiol (E2) and FBG levels (P<0.05), lowered the testosterone (T), triiodothyronine (T3), and tetraiodothyronine (T4) levels (P<0.05), and weakened the renal function (P<0.05). In addition, the modeling led to glomerular hypertrophy and glomerular mesangial and basal thickening, decreased the catalase (CAT) activity, total antioxidant capacity (T-AOC), and glutathione (GSH) content (P<0.05), increased the malondialdehyde (MDA) content (P<0.05), and down-regulated the mRNA and protein levels of Nrf2, HO-1, GCLC, and GPX4 in the renal tissue (P<0.05). Compared with the model group, high and medium doses of Zhenwutang decreased the TCM syndrome score and E2 content (P<0.05), increased the T, T3, and T4 content (P<0.05), improved the renal function (P<0.05), alleviated the pathological changes in the renal tissue, increased CAT, T-AOC, and GSH (P<0.05), reduced MDA (P<0.05), and up-regulated the mRNA and protein levels of Nrf2, HO-1, GCLC, and GPX4 in the renal tissue (P<0.05). ConclusionZhenwutang can improve the general state and renal function and reduce the oxidative damage and pathological changes in the renal tissue of db/db mice with spleen-kidney Yang deficiency by regulating the Nrf2/HO-1/GPX4 signaling pathway.
6.Effect of Buzhong Yiqitang on Th17/Treg Immune Imbalance and Notch1 Signaling Pathway in AIT Mice
Zhuo ZHAO ; Nan SONG ; Ziyu LIU ; Pin LI ; Yue LUO ; Pengkun ZHANG ; Zhimin WANG ; Yuanping YIN ; Tianshu GAO ; Zhe JIN ; Xiao YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):19-27
ObjectiveTo explore the effect of Buzhong Yiqitang on the immune imbalance of helper T cell 17 (Th17)/regulatory T cell (Treg) and Notch1 signaling pathway in mice with autoimmune thyroiditis (AIT). MethodA total of 60 8-week-old NOD.H-2h4 mice were randomly divided into the normal group, model group, western medicine group (selenium yeast tablet, 32.5 mg·kg-1), and low-dose (4.78 g·kg-1·d-1), middle-dose (9.56 g·kg-1·d-1), and high-dose (19 g·kg-1·d-1) Buzhong Yiqitang groups, with 10 mice in each group. The normal group was fed with distilled water, and the other groups were fed with water containing 0.05% sodium iodide for eight weeks. After the animal model of AIT was formed spontaneously, the mice were killed under anesthesia after intragastric administration for eight weeks. Serum anti-thyroglobulin antibodies (TGAb), thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroid hormone (FT4) were detected by enzyme-linked immunosorbent assay (ELISA), and thyroid tissue changes were observed by hematoxylin-eosin (HE) staining. The mRNA and protein expressions of retinoid-related orphan receptor-γt (RORγt), interleukin (IL)-17, forkhead box P3 (FoxP3), IL-10, Notch1, and hair division-related enhancer 1 (Hes1) in thyroid tissue were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot, respectively. ResultCompared with the normal group, the thyroid structure of the model group was severely damaged, and lymphocytes were infiltrated obviously. The levels of serum TGAb, FT3, and FT4 contents were significantly increased, and TSH content was significantly decreased (P<0.01). The mRNA and protein expression levels of RORγt, IL-17, Notch1, and Hes1 were significantly increased, while those of FoxP3 and IL10 were significantly decreased in the model group (P<0.01). Compared with the model group, thyroid structural damage and lymphocyte infiltration were improved in the treatment groups, and serum TGAb, FT3, and FT4 contents were significantly decreased. TSH content was increased, and mRNA and protein expression levels of RORγt, IL-17, Notch1, and Hes1 were decreased. mRNA and protein expression levels of FoxP3 and IL-10 were increased to different degrees (P<0.05, P<0.01), and the middle-dose Buzhong Yiqitang group had the most significant intervention effect. ConclusionBuzhong Yiqitang can alleviate the thyroid structural damage in AIT mice, and its mechanism may be related to improving the abnormal differentiation of Th17/Treg immune cells and inhibiting the activation of the Notch1 signaling pathway.
7.Optimization of Decoction Technology and Establishment of Quality Standard for Moringa oleifera Leaf Standard Decoction
Yanan SONG ; Yun WANG ; Hongjun YANG ; Zhe JIA ; Cun ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(6):151-159
ObjectiveBased on response surface methodology combined with principal component analysis(PCA), the optimal decocting process of Moringa oleifera leaf standard decoction was optimized, and its multi-index quality evaluation system was established, in order to provide scientific basis for the quality control of this standard decoction. MethodResponse surface methodology and PCA were used to optimize the decoction process by taking the relative peak areas of 8 characteristic peaks and dry extract yield as indexes. Based on this, the quality of 15 batches of the standard decoction was evaluated by high performance liquid chromatography(HPLC) characteristic chromatogram, determination of major components(neochlorogenic acid, L-tryptophan, cryptochlorogenic acid, vicenin-2, isoquercetin, astragalin), determination of active parts(total flavonoids, total organic acids, total polysaccharides, total α-amino acids, total sinapine), dry extract yield, specific gravity and pH. ResultThe optimal decocting process was to soak M. oleifera leaves(100.00 g) for 30 min and decoct twice with the first decoction of 12 times the amount of water for 30 min and the second decoction of 10 times the amount of water for 20 min. Standard decoction containing 0.2 g·mL-1 of crude drug was defined by
8.Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults (version 2024)
Qingde WANG ; Yuan HE ; Bohua CHEN ; Tongwei CHU ; Jinpeng DU ; Jian DONG ; Haoyu FENG ; Shunwu FAN ; Shiqing FENG ; Yanzheng GAO ; Zhong GUAN ; Hua GUO ; Yong HAI ; Lijun HE ; Dianming JIANG ; Jianyuan JIANG ; Bin LIN ; Bin LIU ; Baoge LIU ; Chunde LI ; Fang LI ; Feng LI ; Guohua LYU ; Li LI ; Qi LIAO ; Weishi LI ; Xiaoguang LIU ; Hongjian LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Yong QIU ; Limin RONG ; Yong SHEN ; Huiyong SHEN ; Jun SHU ; Yueming SONG ; Tiansheng SUN ; Yan WANG ; Zhe WANG ; Zheng WANG ; Hong XIA ; Guoyong YIN ; Jinglong YAN ; Wen YUAN ; Zhaoming YE ; Jie ZHAO ; Jianguo ZHANG ; Yue ZHU ; Yingjie ZHOU ; Zhongmin ZHANG ; Wei MEI ; Dingjun HAO ; Baorong HE
Chinese Journal of Trauma 2024;40(2):97-106
Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.
9.A novel anchor-loop internal fixation system in coracoclavicular ligament reconstruction for acromioclavicular dislocation: a biomechanical study
Chen WANG ; Na YANG ; Lisong HENG ; Wei FAN ; Yangjun ZHU ; Kun ZHANG ; Zhe SONG
Chinese Journal of Orthopaedic Trauma 2024;26(2):125-129
Objective:To explore the biomechanical stability of a novel anchor-loop internal fixation system in the treatment of acromioclavicular joint dislocation using cadaveric specimens.Methods:The acromioclavicular ligaments were severed in 12 complete shoulder joint specimens, in which the quasi-static non-destructive cycle experiment was performed until the coracoclavicular ligaments failed. The failure intensities of the coracoclavicular ligaments were recorded. Next, the 12 specimens were randomly divided into groups A, B, C and D ( n=3), in which 4 different internal fixation materials were used respectively to reduce and fix the acromioclavicular joint. Group A was subjected to 3.5 mm clavicular hook locking compression plate, group B to 5 mm soft tissue with wire anchor, group C to 10 mm Endobutton steel plate, and group D to the novel anchor-loop internal fixation system (5 mm soft tissue with wire anchor + 10 mm Endobutton steel plate). An X-ray machine was used to evaluate the reduction and internal fixation of the acromioclavicular joint. After the shoulder specimens were securely fastened by a homemade fixation jig to a 100 KN electronic universal mechanical testing machine, each experimental specimen was subjected to a destructive static tensile mechanic determination in the vertical direction at a loading speed of 100 mm/min. The load-displacement curves were recorded and drawn by a computer connected with the biomechanical testing machine. The failure strength and failure causes were recorded for each internal fixation. Results:The fracture strength of the coracoclavicular ligament in 12 cadaver specimens was (374.6±0.8) N. The mechanical load of internal fixation failure was (409.5±2.6) N in group A, (297.8±3.4) N in group B, (375.2±3.1) N in group C and (376.2±3.1) N in group D. The internal fixation failure was due to clavicular fracture in 2 specimens and to acromial fracture in 1 specimen in group A, to anchor protrusion in all the 3 specimens in group B, to coracoid base fracture in all the 3 specimens in group C, and to anchor protrusion in all the 3 specimens in group D. The mechanical loads of internal fixation failure were significantly different among the 4 experimental groups ( P<0.05). The mechanical load of internal fixation failure in group D was significantly different from that in groups A and B ( P<0.05). Conclusions:Our self-developed novel anchor-loop internal fixation system can effectively reposit the acromioclavicular joint to treat acromioclavicular joint dislocation, because it conforms to the biomechanical characteristics of the acromioclavicular joint, and is easy to handle. Therefore, its feasibility is high.
10.Effect of Modified Simiaosan on miR-223-3p and NLRP3/IL-1β Signaling Pathway in Rats with Acute Gouty Arthritis
Mingrui DU ; Zhe SONG ; Huayan LI ; Xin WANG ; Yan CUI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(14):63-70
ObjectiveTo investigate the effect of modified Simiaosan on miR-223-3p and NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/interleukin-1β (IL-1β) signaling pathway in rat model with acute gouty arthritis (AGA) and explore the anti-inflammatory mechanism of modified Simiaosan on AGA. MethodA total of 72 8-week-old male SD rats were selected. They were divided into blank group, model group, colchicine group (0.3 mg·kg-1), high-dose modified Simiaosan group (31.75 g·kg-1), medium-dose modified Simiaosan group (15.75 g·kg-1), and low-dose modified Simiaosan group (7.875 g·kg-1) according to random number table method, with 12 rats in each group. Except for the blank group, monosodium urate (MSU) crystal suspension was injected into the right ankle joint of rats by the Coderre method in other groups to replicate the rat model with AGA. The drug administration groups were given the corresponding drug solution by gavage, and the model group and the blank group were given an equal volume of sterile sodium chloride solution by gavage for one week. The circumference of the rats' ankle joint was measured, and the swelling degree of the ankle joint was calculated. Hematoxylin-eosin (HE) staining was used to detect the pathological morphological changes in the synovial tissue of the ankle joint. The levels of IL-1β, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the serum of rats in each group were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the protein expressions of NLRP3, Caspase-1, and apoptosis-related spot-like protein (ASC) in synovial tissue of rats in each group, and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expressions of NLRP3, Caspase-1, and ASC and the expression of miR-223-3p in synovial tissue of rats. ResultCompared with that in the normal group, the swelling degree of the ankle joint in the model group was higher (P<0.01), and the synovial tissue structure was disordered. Synovial cells proliferated obviously, and a large number of inflammatory cells were infiltrated. The levels of IL-1β, IL-6, and TNF-α in the serum of the model group increased significantly (P<0.01), and the protein and mRNA expressions of NLRP3, Caspase-1, and ASC increased, while expression of miR-223-3 decreased. Compared with the model group, the swelling degree of ankle joint in the colchicine group and high-dose and medium-dose modified Simiaosan groups was lower (P<0.05). Synovial cell proliferation and inflammatory cell infiltration of the colchicine group and high-dose, medium-dose, and low-dose modified Simiaosan groups were reduced to varying degrees, among which the colchicine group and high-dose modified Simiaosan group improved most obviously. The levels of IL-1β, IL-6, and TNF-α in the serum of rats in different dose groups of modified Simiaosan and colchicine group decreased significantly (P<0.01), while the protein and mRNA expressions of NLRP3, Caspase-1, and ASC increased (P<0.01). The expression of miR-223-3p in synovial tissue of the medium-dose and high-dose modified Simiaosan groups and colchicine group increased significantly (P<0.01). Compared with those in the colchicine group, the levels of IL-1β, IL-6, and TNF-α in the low-dose modified Simiaosan group increased greatly (P<0.01). In the medium-dose modified Simiaosan group, the protein expressions of NLRP3, Caspase-1, and ASC increased, and the expression of miR-223-3p decreased (P<0.05). In the low-dose modified Simiaosan group, the levels of IL-1β, IL-6, and TNF-α increased greatly (P<0.01), as well as the protein and mRNA expressions of NLRP3, Caspase-1, and ASC, while the expression of miR-223-3p was decreased (P<0.01). ConclusionModified Simiaosan may play an anti-inflammatory role by intervening in the NLRP3/IL-1β signaling pathway via regulating miR-223-3p.

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