1.Relationship Between Gastroesophageal Reflux Disease-Related Symptoms and Clinicopathologic Characteristics and Long-Term Survival of Patients with Esophageal Adenocarcinoma in China
Kan ZHONG ; Xin SONG ; Ran WANG ; Mengxia WEI ; Xueke ZHAO ; Lei MA ; Quanxiao XU ; Jianwei KU ; Lingling LEI ; Wenli HAN ; Ruihua XU ; Jin HUANG ; Zongmin FAN ; Xuena HAN ; Wei GUO ; Xianzeng WANG ; Fuqiang QIN ; Aili LI ; Hong LUO ; Bei LI ; Lidong WANG
Cancer Research on Prevention and Treatment 2025;52(8):661-665
Objective To investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of
2.Efficacy and safety of transhepatic arterial chemoembolization combined with tyrosine kinase inhibitor and programmed death receptor-1 inhibitors in the treatment of intermediate and a-dvanced unresectable hepatocellular carcinoma
Jianwei XIONG ; Qiang LI ; Tao TANG ; Lixin ZHANG ; Bao YING ; Kaifeng ZHAO ; Yongfu XIONG ; Jingdong LI ; Guo WU
Journal of Clinical Surgery 2024;32(2):176-181
Objective To investigate the clinical effect of transhepatic arterial chemoembolization(TACE)combined with tyrosine kinase inhibitors(TKIs)and programmed death receptors-1(PD-1)inhibitors(TACE+TKIs+PD-1 antibody)in the treatment of moderate advanced unresectable hepatocellular carcinoma(HCC).Methods The clinical data of 65 patients with moderate advanced unresectable hepatocellular carcinoma admitted to the Affiliated Hospital of North Sichuan Medical College from January 2020 to January 2022 were analyzed retrospectively.65 patients were treated with TACE+TKIs+PD-1 antibody.The observation indexes were tumor response,objective response rate(ORR),disease control rate(DCR),total survival time,progression free survival time,conversion operation rate and adverse drug reaction.Results The ORR of 65 p-atients with hepatocellular carcinoma was 49.2%(32/65),and the DCR was 89.2%(58/65).Among them,there were 2 patients with complete remission(CR),30 patients with partial remission(PR),26 patients with stable disease(SD),and 7 patients with progression disease(PD).Among 65 patients with hepatocellular carcinoma,18 patients were transformed into resectable hepatocell-ular carcinoma and underwent RO surgery.The conversion rate was 27.6%(18/65).65 patients were followed up for 3 to 22.4 months,The median follow-up time was 16.5 months.The median overall survival time and median disease progression free survival time of 65 patients were 14.5 months(95%CI:12.3~16.6 months)and 8.8 months(95%CI:6.9~10.6 months),respectively.After treatment,65 patients all had post embolism syndrome(abdominal pain,fever,nausea,vomiting and other symptoms),and some patients had transient abnormal liver function.Adverse drug reactions below grade 3 recovered within a few days.Some patients were associated with multiple adverse drug reactions.1 patient(1.5%)stopped using TACE because of stubborn vomiting,and 5 patients(7.6%)stopped using Lenvatinib because of severe liver function damage during treatment,2 patients(3%)stopped using Camrelizumab because of severe reactive capillary hyperplasia,one patient(1.5%)stopped using Tislelizumab because of severe hypothyroidism,one patient(1.5%)stopped the treatment of Lenvatinib and Sintilimab due to severe gastrointestinal bleeding.The adverse drug reactions of grade 3~4 occurred in other patients were alleviated after drug reduction,symptomatic treatment and hormone treatment.Conclusion TACE+TKIs+PD-1 antibody can obtain reliable clinical efficacy and anti-tumor activity in the treatment of moderate advanced unresectable hepatocellular carcinoma.
3.Expert consensus on pediatric orthodontic therapies of malocclusions in children
Zhou CHENCHEN ; Duan PEIPEI ; He HONG ; Song JINLIN ; Hu MIN ; Liu YUEHUA ; Liu YAN ; Guo JIE ; Jin FANG ; Cao YANG ; Jiang LINGYONG ; Ye QINGSONG ; Zhu MIN ; Jiang BEIZHAN ; Ruan WENHUA ; Yuan XIAO ; Li HUANG ; Zou RUI ; Tian YULOU ; Gao LI ; Shu RUI ; Chen JIANWEI ; Liu RENKAI ; Zou SHUJUAN ; Li XIAOBING
International Journal of Oral Science 2024;16(2):186-196
Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of~260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.
4.Expression and clinical significance of long non-coding RNA differentially expressed genes, micro RNA-181a-5p and autophagy-related protein 5 in primary gouty arthritis
Jianwei GUO ; Tianyi LEI ; Peng WANG ; Zeng ZHANG ; Guilin JIAN ; Quanbo ZHANG ; Yufeng QING
Chinese Journal of Rheumatology 2024;28(5):303-311
Objective:To explore the expression and clinical significance of long non-coding RNA colorectal neoplasia differentially expressed (lncRNA CRNDE), microRNA-181a-5p (miR-181a-5p) and autophagy related 5 (ATG5) in the peripheral blood of patients with gouty arthritis (GA) patients.Methods:The clinical data, laboratory parameters and peripheral blood samples were collected from 40 patients with acute gout (AG), 40 patients with intermittent gout (IG) and 50 healthy subjects (HC). The expression levels of lncRNA CRNDE, miR-181a-5p and ATG5 mRNA were detected by real-time fluorescence quantification (RT-qPCR) and the expression level of ATG5 protein was detected by Western-blot. The expression levels of lncRNA CRNDE, miR-181a-5p, ATG5 mRNA were compared among the three groups and correlated with clinical indices, and a subject operating characteristic curve (ROC) was constructed to assess the value of lncRNA CRNDE, miR-181a-5p, ATG5 mRNA in the diagnosis of gout. Measurements conforming to normal distribution were analyzed using t test or ANOVA, data with non-normal distribution was analyzed using Mann-Whitney U test or Kruskal-Wallis H test, correlation analysis between variables was analyzed using Spearman's analysis, and the diagnostic value of each indicator was analyzed using ROC curve. Results:① The differences in the expression of lncRNA CRNDE, miR-181a-5p, and ATG5 mRNA between the three groups were statistically significant ( H=32.12, 57.73, 68.32, all P<0.001). Among them, lncRNA CRNDE expression level in the AG group was significantly higher than that in the IG group and healthy control group [61.95(11.39, 108.30)×10 -3, 25.71(15.40, 38.40)×10 -3, 13.80(3.97, 23.99)×10 -3; Z=-3.24, P=0.001; Z=-5.03, P<0.001], and the expression level of IG group was higher than that of healthy control group( Z=-3.56, P<0.001); miR-181a-5p and ATG5 mRNA expression levels in AG group were significantly lower than those in IG group and healthy control group [miR-181a-5p: 39.81(31.22, 69.38)×10 -3, 60.74(44.19, 90.35)×10 -3, 121.30(101.50, 316.90)×10 -3; Z=-3.01, P=0.030; Z=-6.93, P<0.001. ATG5 mRNA: 4.52(2.31, 26.63)×10 -3, 43.63(13.72, 102.70)×10 -3, 153.90(66.62, 365.80)×10 -3; Z=-5.47, -7.36, all P<0.001)], which were expressed at lower levels in the IG group than in the healthy controls ( Z=-5.25, -4.47, all P<0.001). The difference of ATG5 protein expression level among the three groups expressed was statistically significant ( F=6.24, P=0.030), and the AG group was higher than the healthy control group, and the difference was statistically significant [(0.96±0.13) vs.(0.61±0.04), t=4.25, P=0.013], but the difference between the IG group (0.78±0.15) and the AG group and the HC group was not statistically significant ( t=1.51, P=0.206; t=1.85, P=0138). ② Spearman correlation analysis showed that lncRNA CRNDE was negatively correlated with the expression levels of miR-181a-5p and ATG5 mRNA in gout patients ( r=-0.49, P<0.001; r=-0.35, P=0.002); miR-181a-5p was positively correlated with ATG5 mRNA expression levels ( r=0.64, P<0.001); lncRNA CRNDE expression level was positively correlated with ESR and WBC ( r=0.49, P<0.001; r=0.43, P=0.001); miR-181a-5p expression level was negatively correlated with ESR and WBC ( r=-0.29, P=0.009; r=-0.35, P=0.002), and ATG5 mRNA expression levels were negatively correlated with ESR, WBC, and GR ( r=-0.26, P=0.021; r=-0.26, P=0.024; r=-0.27, P=0.021). In the AG group lncRNA CRNDE was positively correlated with ESR and WBC ( r=0.36, P=0.022; r=0.36, P=0.026) and miR-181a-5p was negatively correlated with WBC ( r=-0.34, P=0.038) ③ ROC curve showed that the areas under ROC curve of lncRNA CRNDE, miR-181a-5p and ATG5 mRNA expression levels to predict gout were 0.764, 0.875 and 0.864, respectively. The area under ROC curve of gout predicted by the three combined was 0.928. Conclusion:lncRNA CRNDE, miR-181a-5p, and ATG5 may be involved in the pathoge-nesis of primary gouty arthritis, and are potential biological parameters for studying the pathogenesis of gout.
5.Expression level and clinical significance of autophagy related genes in peripheral blood mononuclear cells of patients with refractory moderate-to-severe rheumatoid arthritis treated with abatacept
Qian HUANG ; Tao LI ; Yan XIE ; Zeng ZHANG ; Jianwei GUO ; Quanbo ZHANG ; Yufeng QING
Chinese Journal of Rheumatology 2024;28(11):796-802
Objective:To investigate and explore the clinical significance of the expression levels and differences of autophagy related genes ATG3, ATG5, ATG12, ATG16, LC3 and Beclin-1 in peripheral blood mononuclear cells of patients with refractory moderate-to-severe rheumatoid arthritis (RA), who were treated with abatacept.Methods:Peripheral blood samples of 30 patients admitted to the affiliated hospital of North Sichuan Medical College from June 2020 to June 2022 were collected before and after abatacept treatment. Autophagy associated genes were detected by RT-qPCR and, autophagy associated proteins were detected by Western Blot. Correlation analysis with clinical parameters was performed. SPSS26.0 and GraphPad Prism 9.0 were used for statistical analysis, Independent sample t-test was used for comparison between groups, and non-normal distribution data were expressed as M ( Q1, Q3), Spearman correlation analysis was used to analyze the correlation between variables, and P<0.05 was considered statistically significant. Results:①Compared with the mRNA expression levels of ATG12(0.007 6±0.005 9), ATG16(0.003 1±0.002 2) and LC3(0.038 2±0.017 1) before treatment, after 24 weeks treatment with abatacept, the mRNA expression levels of ATG12 (0.011 4±0.003 1) and ATG16 (0.004 2±0.000 7) increased ( t=-2.49, P=0.042; t=-2.15, P=0.038), and the mRNA expression level of LC3 (0.022 6±0.008 3) was decreased ( t=3.28, P=0.003) after 24 weeks of abatacept treatment.②After 24 weeks, the expression level of ATG16 mRNA in the remission group (0.004 8±0.000 8) was higher than that in the non-remission group (0.003 8±0.000 3) ( t=-3.41, P=0.003). The expression level of LC3 mRNA in remission group (0.027 3±0.007 3) was lower than that in non-remission group (0.017 9±0.006 5) ( t=3.69, P=0.017). ③ATG5 mRNA expression level was positively correlated with TJC, ESR and anti-CCP antibody ( r=0.75, P=0.049; r=0.43, P=0.044; r=0.97, P=0.011). The expression level of ATG12 mRNA was negatively correlated with DAS28, ESR and hsCRP ( r=-0.46, P=0.025; r=-0.51, P=0.026; r=-0.41, P=0.031). The expression level of ATG16 mRNA was positively correlated with ESR and hsCRP ( r=0.50, P=0.030; r=0.40, P=0.024). The expression level of Beclin-1 mRNA was significantly higher than TJC, RF-IgG and anti-CCP antibody were negatively correlated ( r=-0.51, P=0.025; r=-0.42, P=0.035; r=-0.81, P=0.043). The expression level of LC-3 mRNA was positively correlated with ESR and hsCRP ( r=0.55, P=0.028; r=0.56, P=0.024). ④Compared with the protein expression level before the treatment, of ATG12 (0.675 3±0.036 3), which (1.547 7±0.080 5) increased after 24 weeks of treatment ( t=-7.80, P=0.001). Compared with the protein expression levels of ATG16 (0.817 1±0.089 0), LC3Ⅱ (0.807 1±0.072 1) and IL-1β (1.129 7±0.118 9) before treatment, 24 weeks after, the protein expression levels of ATG16 (0.424 6±0.103 5), LC3Ⅱ (0.353 7±0.056 9) and IL-1β (0.346 7±0.050 8) decreased ( t=2.62, P=0.042; t=2.88, P=0.045; t=2.25, P=0.038) 24 weeks after treatment. Conclusion:Autophagy related genes is associated with several clinical presentations and disease activity. The results of this study suggest that autophageius are involved in the pathogenesis of RA. Abatacept may be a potential autophage modulator by regulating autophagy related genes including ATG12、ATG16 and LC3.
6.Value of deep learning technology for the differential diagnosis of endoscopic ultrasonography images of gastrointestinal stromal tumors and leiomyomas
Kangli GUO ; Jianwei ZHU ; Zhanghao HUANG ; Chunping LIU ; Duanmin HU
Chinese Journal of Digestive Endoscopy 2024;41(6):449-454
Objective:To construct a classification model for endoscopic ultrasonography (EUS) images of gastrointestinal stromal tumors (GISTs) and leiomyomas (LM) based on deep learning technology, and to verify its value for differential diagnosis.Methods:From October 2014 to October 2021, 69 patients of GISTs and 73 of LM who underwent EUS and were pathologically confirmed by surgery or endoscopic resection in the Second Affiliated Hospital of Soochow University were retrospectively studied. One clear EUS image with typical lesion was selected for each case. Using the hold-out method, the images of each disease were divided into the training set and the validation set according to the ratio of the number of images in the training set to the number of images in the validation set, which was 8∶2. Finally, 113 EUS images (55 GISTs and 58 LM) were used to form the training set, and 29 EUS images (14 GISTs and 15 LM) were used to form the validation set. The training set was used to train and optimize the deep learning model, and the validation set was used to verify the classification model. The main observation indicators included the sensitivity, the specificity, the positive predictive value, the negative predictive value and the accuracy of differential diagnosis.Results:The accuracy of the classification model established by Resnet 34 network structure in the differential diagnosis of GISTs and LM tended to be 0.89, better than the classification model established by Resnet 50 network structure (0.81). The sensitivity, the specificity, the positive predictive value, the negative predictive value and the accuracy of the classification model based on Resnet 34 network structure for differentiating EUS images in the validation set were 85.71% (12/14, 95% CI: 67.38%-100.00%), 93.33% (14/15, 95% CI: 80.71%-100.00%), 92.31% (12/13, 95% CI: 77.82%-100.00%), 87.50% (14/16, 95% CI: 71.30%-100.00%) and 89.66% (26/29, 95% CI: 78.57%-100.00%), respectively. Conclusion:It is feasible to use deep learning technology in the differential diagnosis of EUS images of GISTs and LM, which can provide auxiliary diagnostic opinions for clinicians. The deep learning model based on Resnet 34 network structure shows higher accuracy in the differential diagnosis of EUS images of GISTs and LM.
7.Long non-coding RNA CTC-338M12.4 inhibition on activation of JAK/STAT signaling pathway via miRNA-27a-5p makes cell cycle arrest, cell proliferation and migration inhibition in tongue squamous cell carcinoma
Xin PENG ; Jin WANG ; Yan XIONG ; Xiaoquan LUO ; Hui GUO ; Jianwei PENG
Cancer Research and Clinic 2024;36(11):801-807
Objective:To investigate the expression level of long non-coding RNA (lncRNA) CTC-338M12.4 in tongue squamous cell carcinoma tissues, and its effects on the cell cycle, cell proliferation, and migration of tongue squamous cell carcinoma cells in vitro as well as its molecular mechanisms.Methods:The Gene Expression Omnibus (GEO) database was used to obtain the lncRNA series data set GSE139869, and the differential expression of CTC-338M12.4 in tongue squamous cell carcinoma tissues and adjacent tissues was analyzed. The transcriptional expression levels of CTC-338M12.4 in human immortalized oral keratinocytes (HOK) and tongue squamous cell carcinoma cell lines HN13, TSCCa, CAL-27, Tca8113, SCC15 were detected by using reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR). CAL-27 cells with the lowest expression level of CTC-338M12.4 were selected and were divided into the control group (co-transfected with vectors containing negative sequence) and CTC-338M12.4 group (co-transfected with CTC-338M12.4 overexpression vectors). The proliferation ability of CAL-27 cells in each group was detected by using cell colony formation assay, and the cell cycle distribution of CAL-27 cells was detected by using flow cytometry. The migration ability of CAL-27 cells was detected by using scratch test. The lncACTdb database was used to predict the complementary binding sites between CTC-338M12.4 and miRNA-27a-5p (miR-27a-5p), and dual-luciferase reporter gene assay was used to verify. The expression level of miR-27a-5p in CAL-27 cells of all groups was detected by using qRT-PCR. The protein expression level of related factors on JAK/STAT signaling pathway in CAL-27 cells of all groups was detected by using Western blot.Results:Analysis of GEO database data showed that transcriptional level CTC-338M12.4 in tongue squamous cell carcinoma tissues was lower than that in adjacent tissues, and the difference was statistically significant ( P < 0.01). Transcriptional level CTC-338M12.4 in tongue squamous cell carcinoma HNl3, TSCCa, CAL-27, Tca8113, and SCC15 cells was lower than that in HOK cells, and the differences were statistically significant (all P < 0.05). The transcriptional level relative expression level of CTC-338M12.4 in CAL-27 cells in the CTC-338M12.4 group was higher than that in the control group, and the difference was statistically significant ( P < 0.01). Cell colony formation assay showed that the colong number of CAL-27 cell in the CTC-338M12.4 group was less than that in the control group [(51±10) vs. (114±21)], and the difference was statistically significant ( t = 2.71, P = 0.035). Flow cytometry showed that the proportion of G 0/G 1 phase cells in CAL-27 cells in the CTC-338M12.4 group was higher than that in the control group [(64±3)% vs. (43±4)%], and the difference was statistically significant ( t = 4.87, P = 0.003). The scratch test showed that when scratching, the scratch width of both groups was similar ( P > 0.05); after scratch for 25 h, the scratch width of CAL-27 cells in the CTC-338M12.4 group was wider than that in the control group [(133±15) μm vs. (64±10) μm], and the difference was statistically significant ( t = 3.78, P = 0.009). The dual luciferase reporter gene assay showed that the relative luciferase activity of CAL-27 cells co-transfected with wild-type CTC-338M12.4 sequence and miR-27a-5p sequence was lower than that of CAL-27 cells co-transfected with wild-type CTC-338M12.4 sequence and miR-27a-5p irrelevant sequence, and the difference was statistically significant ( P < 0.001). The relative expression level of transcriptional level miR-27a-5p of CAL-27 cells in the CTC-338M12.4 group was lower than that in the control group, and the difference was statistically significant ( P = 0.003). Western blot showed that the protein expression levels of JAK/STAT signaling pathway p-JAK, p-STAT, p-Raf, p-ERK, and p-mTOR were lower than those in the control group. Conclusions:The level of lncRNA CTC-338M12.4 is low in tongue squamous cell carcinoma. CTC-338M12.4 mediates the inactivation of JAK/STAT signaling pathway via inhibiting miR-27a-5p expression in tongue squamous cell carcinoma CAL-27 cells, thereby leading to cell cycle arrest and inhibiting the cell proliferation and migration of CAL-27 cells.
8.Advancing drug delivery to articular cartilage: From single to multiple strategies.
Tianyuan ZHAO ; Xu LI ; Hao LI ; Haoyuan DENG ; Jianwei LI ; Zhen YANG ; Songlin HE ; Shuangpeng JIANG ; Xiang SUI ; Quanyi GUO ; Shuyun LIU
Acta Pharmaceutica Sinica B 2023;13(10):4127-4148
Articular cartilage (AC) injuries often lead to cartilage degeneration and may ultimately result in osteoarthritis (OA) due to the limited self-repair ability. To date, numerous intra-articular delivery systems carrying various therapeutic agents have been developed to improve therapeutic localization and retention, optimize controlled drug release profiles and target different pathological processes. Due to the complex and multifactorial characteristics of cartilage injury pathology and heterogeneity of the cartilage structure deposited within a dense matrix, delivery systems loaded with a single therapeutic agent are hindered from reaching multiple targets in a spatiotemporal matched manner and thus fail to mimic the natural processes of biosynthesis, compromising the goal of full cartilage regeneration. Emerging evidence highlights the importance of sequential delivery strategies targeting multiple pathological processes. In this review, we first summarize the current status and progress achieved in single-drug delivery strategies for the treatment of AC diseases. Subsequently, we focus mainly on advances in multiple drug delivery applications, including sequential release formulations targeting various pathological processes, synergistic targeting of the same pathological process, the spatial distribution in multiple tissues, and heterogeneous regeneration. We hope that this review will inspire the rational design of intra-articular drug delivery systems (DDSs) in the future.
9.Immunogenicity of mucosal COVID-19 vaccine candidates based on the highly attenuated vesicular stomatitis virus vector (VSVMT) in golden syrian hamster.
Yong KE ; En ZHANG ; Jianming GUO ; Xiaoxiao ZHANG ; Lei WANG ; Duo CHEN ; Xinkui FANG ; Jianwei ZHU ; Feng LI ; Tao SUN ; Baohong ZHANG
Acta Pharmaceutica Sinica B 2023;13(12):4856-4874
COVID-19 is caused by coronavirus SARS-CoV-2. Current systemic vaccines generally provide limited protection against viral replication and shedding within the airway. Recombinant VSV (rVSV) is an effective vector which inducing potent and comprehensive immunities. Currently, there are two clinical trials investigating COVID-19 vaccines based on VSV vectors. These vaccines were developed with spike protein of WA1 which administrated intramuscularly. Although intranasal route is ideal for activating mucosal immunity with VSV vector, safety is of concern. Thus, a highly attenuated rVSV with three amino acids mutations in matrix protein (VSVMT) was developed to construct safe mucosal vaccines against multiple SARS-CoV-2 variants of concern. It demonstrated that spike protein mutant lacking 21 amino acids in its cytoplasmic domain could rescue rVSV efficiently. VSVMT indicated improved safeness compared with wild-type VSV as the vector encoding SARS-CoV-2 spike protein. With a single-dosed intranasal inoculation of rVSVΔGMT-SΔ21, potent SARS-CoV-2 specific neutralization antibodies could be stimulated in animals, particularly in term of mucosal and cellular immunity. Strikingly, the chimeric VSV encoding SΔ21 of Delta-variant can induce more potent immune responses compared with those encoding SΔ21 of Omicron- or WA1-strain. VSVMT is a promising platform to develop a mucosal vaccine for countering COVID-19.
10.Changes and clinical significance of microRNA-146b and signal transducer and transcriptional activator 1/3 in male primary gouty arthritis
Zeng ZHANG ; Peng WANG ; Jianwei GUO ; Tianyi LEI ; Quanbo ZHANG ; Shaowei NIU ; Xia LIAO ; Yufeng QING
Chinese Journal of Rheumatology 2023;27(6):385-392
Objective:To This study was to investigate the expression and possible clinical significance of microRNA-146b (miR-146b) and signal transducer and transcriptional activator 1 and 3 (STAT1/3) in peripheral blood mononuclear cells (PBMCs) of patients with primary gouty arthritis (GA).Methods:The peripheral blood samples, clinical data and laboratory indexes of 120 male cases of GA [including 57 cases of acute (AG group) and 63 cases of intermittent (IG group)]and 66 healthy subjects (HC group) were collected. The expression levels of miR-146b and STAT1/3 in PBMCs were detected by real-time fluorescence quantitative PCR (RT-qPCR). The differences among the three groups were compared and the correlation between them and clinical indexes was analyzed. The receiver operating characteristic curve (ROC) was constructed to evaluate its diagnostic value in GA. After the PBMCs of 18 healthy subjects were stimulated by 100 μg/ml MSU for 3 hours to simulate acute gout inflammatory environment, the transcriptional changes of IL-1β, miR-146b and STAT1/3 were detected by RT-qPCR, and the expressions of IL-1β, STAT1/3 protein and phosphorylated protein were detected by Western blotting. T test or one-way ANOVA and LSD- t test were used in accordance with the normal measurement data, Kruskal-Wallis H and Mann-Whitney U test were used in the non-normal data, Spearman correlation analysis was used in the correlation between variables, and the diagnostic value was evaluated by the receiver working characteristic curve ROC. Results:①There were statistical differences in the expression of miR-146b, STAT1 and STAT3 among the three groups ( F=7.02、19.52、17.07, all P<0.001). The expression of miR-146b in gout group [(0.32±0.28)] was significantly higher than that in HC group (0.19±0.18)( t=2.96, P=0.003), while STAT1(0.019±0.012) and STAT3(0.014±0.010) were significantly lower than those in HC group (0.038±0.029),(0.025±0.016)( t=6.26, 5.56, both P<0.001). Further subgroup analysis showed that the expression of miR-146b in AG and IG groups was higher than that in HC group[(0.27±0.17), (0.38±0.35), (0.19±0.18), t=2.09, 3.30, both P<0.05], but that in AG group was lower than that in IG group ( t=2.02, P<0.05). The expression of STAT1 mRNA in AG and IG groups was lower than that in HC group [(0.020±0.012), (0.019±0.012), (0.038±0.029), t=4.89, 4.56, both P<0.001], but there was no statistical significance between AG and IG groups ( t=0.24, P>0.05). The expression of STAT3 mRNA in AG and IG groups was lower than that in HC group [(0.016±0.012), (0.012±0.008), (0.025±0.016), t=5.64, 3.33, both P<0.01], and the expression of STAT3 mRNA in AG group was higher than that in IG group ( t=2.12, P<0.05). ② Spearman correlation analysis showed that the expression of miR-146b in GA was negatively correlated with HCY ( r=-0.37, P=0.014), STAT1 was negatively correlated with Crea ( r=-0.29, P=0.019), positively correlated with eGFR ( r=0.25, P=0.047), and STAT3 was negatively correlated with HDL-C ( r=-0.27, P=0.033). ③ROC curve showed that the AUC (95% CI) of miR-146b, STAT1 and STAT3 were 0.679(0.582, 0.776), 0.710(0.629, 0.791) and 0.705(0.626, 0.783), and the combined AUC(95% CI) of the three was 0.836 (0.765, 0.907). ④Compared with blank control group and negative control group, the expression of miR-146b in PBMCs of 18 cases of HC was significantly decreased ( H=14.44, P=0.003), while the expression of IL-1β, STAT1 and STAT3 mRNA was significantly increased after 3 h of MSU stimulation ( H=26.44、27.26、15.90, all P<0.001). The expression of IL-1β, STAT1 and STAT3 protein and phosphorylated protein in the model group were significantly higher than those in the blank control group, and the differences were statistically significant ( t=9.97、6.63、7.48、11.25、6.28, all P<0.01). Conclusion:The abnormal expression of miR-146b and STAT1/3 in GA is related to some clinical indicators, suggesting that it may be involved in the regulation of gout immune inflammatory response and metabolism, and the specific mechanism is worth further study.

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