1.A multicenter clinical study on intramedullary vancomycin injection for preventing periprosthetic joint infection in total knee arthroplasty
Te LIU ; Jun FU ; Shiguang LAI ; Zhuo ZHANG ; Chi XU ; Lei GENG ; Yang LUO ; Peng REN ; Xin ZHI ; Quanbo JI ; Heng ZHANG ; Runkai ZHAO ; Haichao REN ; Ye TAO ; Qingyuan ZHENG ; Zeyu FENG ; Jianfeng YANG ; Yiming WANG ; Pengcheng LI ; Shuai LIU ; Wei CHAI ; Xiang LI ; Huiwu LI ; Xiaogang ZHANG ; Baochao JI ; Xianzhe LIU ; Xinzhan MAO ; Jianbing MA ; Xiangxiang SUN ; Jiying CHEN ; Yonggang ZHOU ; Jinliang WANG ; Weijun WANG ; Guoqiang ZHANG ; Ming NI
Chinese Journal of Orthopaedics 2025;45(12):803-811
Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.
2.Effect of Cinnamaldehyde on Systemic Candida albicans Infection in Mice.
Xiao-Ru GUO ; Xiao-Guang ZHANG ; Gang-Sheng WANG ; Jia WANG ; Xiao-Jun LIU ; Jie-Hua DENG
Chinese journal of integrative medicine 2025;31(7):644-648
OBJECTIVE:
To investigate the therapeutic efficacy of cinnamaldehyde (CA) on systemic Candida albicans infection in mice and to provide supportive data for the development of novel antifungal drugs.
METHODS:
Ninety BALB/c mice were randomly divided into 3 groups according to a random number table: CA treatment group, fluconazole (positive control) group, and Tween saline (negative control) group, with 30 mice in each group. Initially, all groups of mice received consecutive intraperitoneal injections of cyclophosphamide at 200 mg/kg for 2 days, followed by intraperitoneal injection of 0.25 mL C. albicans fungal suspension (concentration of 1.0 × 107 CFU/mL) on the 4th day, to establish an immunosuppressed systemic Candida albicans infection animal model. Subsequently, the mice were orally administered CA, fluconazole and Tween saline, at 240, 240 mg/kg and 0.25 mL/kg respectively for 14 days. After a 48-h discontinuation of treatment, the liver, small intestine, and kidney tissues of mice were collected for fungal direct microscopic examination, culture, and histopathological examination. Additionally, renal tissues from each group of mice were collected for (1,3)- β -D-glucan detection. The survival status of mice in all groups was monitored for 14 days of drug administration.
RESULTS:
The CA group exhibited a fungal clearance rate of C. albicans above 86.7% (26/30), significantly higher than the fluconazole group (60.0%, 18/30, P<0.01) and the Tween saline group (30.0%, 9/30, P<0.01). Furthermore, histopathological examination in the CA group revealed the disappearance of inflammatory cells and near-normal restoration of tissue structure. The (1,3)-β-D-glucan detection value in the CA group (860.55 ± 126.73 pg/mL) was significantly lower than that in the fluconazole group (1985.13 ± 203.56 pg/mL, P<0.01) and the Tween saline group (5910.20 ± 320.56 pg/mL, P<0.01). The mouse survival rate reached 90.0% (27/30), higher than the fluconazole group (60.0%, 18/30) and the Tween saline group (30.0%, 9/30), with a significant difference between the two groups (both P<0.01).
CONCLUSIONS
CA treatment exhibited significant therapeutic efficacy in mice with systemic C. albicans infection. Therefore, CA holds potential as a novel antifungal agent for targeted treatment of C. albicans infection.
Animals
;
Acrolein/pharmacology*
;
Candida albicans/physiology*
;
Mice, Inbred BALB C
;
Candidiasis/pathology*
;
Antifungal Agents/therapeutic use*
;
Mice
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Fluconazole/therapeutic use*
;
Kidney/drug effects*
;
Female
3.A study on the preference of elderly cancer patients in a certain specialized cancer hospital for online hospital services based on discrete choice experiments
Quanbo HUO ; Xiaotong YANG ; Wei ZHANG ; Xuanyue YAN ; Yaxin FU ; Junqing LIU ; Ling YAN
Modern Hospital 2025;25(6):930-935
Objective To analyze the preferences of elderly cancer patients for internet hospital diagnosis and treatment services,providing a reference for the sustainable development of internet hospitals.Methods This study was based on the method of discrete choice experiments.By combining literature review and expert consultation,10 relevant attributes affecting the choice of internet hospitals by elderly cancer patients were determined.Through KANO questionnaires,6 key attributes were se-lected to form the final DCE questionnaire,consisting of 11 choice sets and 1"quality control"set.Using the convenience sam-pling method,elderly cancer patients visiting a certain tertiary hospital in Tianjin were selected to collect 318 valid question-naires.The obtained data were analyzed using mixed Logit regression.Results Patients visiting a certain specialized cancer hos-pital in Tianjin tend to prefer hospitals with a grade of Grade Ⅲ-A(β=0.661 6,P<0.05)and those offering out-of-hospital rehabilitation guidance for cancer patients(β=0.559 9,P<0.05).The page operation process(β=0.352 2,P<0.05)and the accessibility mode for the elderly(β=0.357 5,P<0.05)are the attributes with lower attention.In the subgroup analysis,for patients of different genders and different family incomes,hospital grade and out-of-hospital rehabilitation guidance for cancer patients remain the most influential factors,but male patients pay more attention to the page operation process(β=0.378 3,P<0.05)and the accessibility mode for the elderly(β=0.373 7,P<0.05),while female patients pay more attention to the cover-age of medical insurance reimbursement(β=0.435 9,P<0.05),which has a greater impact than that of male patients(β=0.394 7,P<0.05);patients with a monthly per capita income of less than 5 000 yuan pay more attention to the coverage of medical insurance reimbursement(β=0.423 0,P<0.05)and the self-appointment check function(β=0.467 0,P<0.05);while patients with a monthly per capita income of more than 5 000 yuan pay more attention to the page operation process(β=0.364 7,P<0.05)and the accessibility mode for the elderly(β=0.359 1,P<0.05).Conclusion Hospitals should en-hance elderly patients' awareness and trust in internet hospitals by providing comprehensive health education and support,simpli-fying operational processes,strengthening age-friendly design,and highlighting medical insurance coverage to address the diverse needs across genders and income levels.
4.A multicenter clinical study on intramedullary vancomycin injection for preventing periprosthetic joint infection in total knee arthroplasty
Te LIU ; Jun FU ; Shiguang LAI ; Zhuo ZHANG ; Chi XU ; Lei GENG ; Yang LUO ; Peng REN ; Xin ZHI ; Quanbo JI ; Heng ZHANG ; Runkai ZHAO ; Haichao REN ; Ye TAO ; Qingyuan ZHENG ; Zeyu FENG ; Jianfeng YANG ; Yiming WANG ; Pengcheng LI ; Shuai LIU ; Wei CHAI ; Xiang LI ; Huiwu LI ; Xiaogang ZHANG ; Baochao JI ; Xianzhe LIU ; Xinzhan MAO ; Jianbing MA ; Xiangxiang SUN ; Jiying CHEN ; Yonggang ZHOU ; Jinliang WANG ; Weijun WANG ; Guoqiang ZHANG ; Ming NI
Chinese Journal of Orthopaedics 2025;45(12):803-811
Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.
5.A study on the preference of elderly cancer patients in a certain specialized cancer hospital for online hospital services based on discrete choice experiments
Quanbo HUO ; Xiaotong YANG ; Wei ZHANG ; Xuanyue YAN ; Yaxin FU ; Junqing LIU ; Ling YAN
Modern Hospital 2025;25(6):930-935
Objective To analyze the preferences of elderly cancer patients for internet hospital diagnosis and treatment services,providing a reference for the sustainable development of internet hospitals.Methods This study was based on the method of discrete choice experiments.By combining literature review and expert consultation,10 relevant attributes affecting the choice of internet hospitals by elderly cancer patients were determined.Through KANO questionnaires,6 key attributes were se-lected to form the final DCE questionnaire,consisting of 11 choice sets and 1"quality control"set.Using the convenience sam-pling method,elderly cancer patients visiting a certain tertiary hospital in Tianjin were selected to collect 318 valid question-naires.The obtained data were analyzed using mixed Logit regression.Results Patients visiting a certain specialized cancer hos-pital in Tianjin tend to prefer hospitals with a grade of Grade Ⅲ-A(β=0.661 6,P<0.05)and those offering out-of-hospital rehabilitation guidance for cancer patients(β=0.559 9,P<0.05).The page operation process(β=0.352 2,P<0.05)and the accessibility mode for the elderly(β=0.357 5,P<0.05)are the attributes with lower attention.In the subgroup analysis,for patients of different genders and different family incomes,hospital grade and out-of-hospital rehabilitation guidance for cancer patients remain the most influential factors,but male patients pay more attention to the page operation process(β=0.378 3,P<0.05)and the accessibility mode for the elderly(β=0.373 7,P<0.05),while female patients pay more attention to the cover-age of medical insurance reimbursement(β=0.435 9,P<0.05),which has a greater impact than that of male patients(β=0.394 7,P<0.05);patients with a monthly per capita income of less than 5 000 yuan pay more attention to the coverage of medical insurance reimbursement(β=0.423 0,P<0.05)and the self-appointment check function(β=0.467 0,P<0.05);while patients with a monthly per capita income of more than 5 000 yuan pay more attention to the page operation process(β=0.364 7,P<0.05)and the accessibility mode for the elderly(β=0.359 1,P<0.05).Conclusion Hospitals should en-hance elderly patients' awareness and trust in internet hospitals by providing comprehensive health education and support,simpli-fying operational processes,strengthening age-friendly design,and highlighting medical insurance coverage to address the diverse needs across genders and income levels.
6.Efficacy and safety of first-line anti-tuberculosis drugs combined with Linezolid for the treatment of pediatric tuberculous meningitis in real-word practice
Ting AI ; Li JIANG ; Quanbo LIU ; Yuan BAI ; Ya YANG ; Fengjun SUN ; Yuntao JIA ; Yujiao ZHOU ; Zhenzhen ZHANG
Chinese Journal of Pediatrics 2024;62(8):715-720
Objective:To evaluate the efficacy and safety of first-line anti-tuberculosis (TB) drugs combined with linezolid in treatment of children with tuberculous meningitis (TBM).Methods:A retrospective cohort study design was performed . Eight-nine Children diagnosed as TBM during January 1 st 2016 and December 31 st 2023 in Department of Infectious Disease, Children′s Hospital of Chongqing Medical University were enrolled in the study. According to different treatment regimens, children were divided into a group of first-line anti-tuberculous drugs (isoniazid, rifampicin, pyrazinamide, ethambutol (HRZE)) and a group of HRZE and linezolid combination (HRZEL). The efficacy and safety of the 2 regimens were compared and the relationship between linezolid drug concentration and adverse reactions were analyzed. Comparisons between groups were performed using χ2 test and Mann-Whitney U test. Results:The 89 children with TBM included 53 males and 36 females with an onset age of 4.6 (1.4, 9.6) years. There were 27 cases in the HZREL group and 62 cases in the HRZE group. Before treatment, positive rate of interferon-gamma release assays (IGRA) in HRZEL group was lower than that in HRZE group (64% (16/25) vs.92% (55/60), χ2=9.82, P<0.05), but protein level of cerebrospinal fluid (CSF) was higher than that in HRZE group (1.2 (1.0, 2.0) vs.0.8 (0.4,1.4) g/L, Z=0.32, P<0.05). By the end of the intensive phase, there were no significant differences of rates of CSF improvement and etiology negativity between HRZEL group and HRZE group (both P>0.05).The 44 TBM children with high CSF protein (>1 g/L) included 25 males and 19 females with an onset age of 6.7 (3.0, 11.8) years. There were 21 cases in the HZREL group and 23 cases in the HRZE group accordingly. Before treatment, there were no significant differences of positive rate of IGRA test and CSF protein level between the 2 groups (62% (13/21) vs. 87% (20/23), 1.7 (1.1, 2.2) vs. 1.5 (1.2, 1.9) g/L, χ2=3.67, Z=0.23, both P>0.05). There were no significant differences in CSF indicators, etiology negativity or imaging remission between the two groups by the end of intensive phase (all P>0.05). Higher frequencies of granulocytopenia, gastrointestinal symptoms as well as withdrawal or change of drugs were found in HRZEL group when compared to those in HRZE group (44% (12/27) vs. 19% (12/62), 7% (2/27) vs. 0, 33% (9/27) vs. 3% (2/62), χ2=6.01, 4.70, 15.74, all P<0.05). Conclusions:The efficacy of HRZEL regimen is similar to conventional HRZE regimen in children with TBM, but with higher adverse effect. Prudentially evaluating the pros and cons of linezolid in the usage of drug-susceptible TB and carefully monitoring of linezolid associated adverse effects is suggested.
7.DcR3 suppresses the NF-κB pathway and the NLRP3 inflammasome activation in gouty inflammation.
Yi JIANG ; Xin TU ; Jianwei GUO ; Jianxiong ZHENG ; Xia LIAO ; Yixi HE ; Yan XIE ; Quanbo ZHANG ; Yufeng QING
Chinese Medical Journal 2024;137(21):2644-2646
8.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.
9.Expression and clinical significance of N6-methyladenosine modification-related genes in peripheral blood mononuclear cells from patients with gouty arthritis
Yanhui LI ; Tianyi LEI ; Yang WANG ; Xin TU ; Mei WANG ; Xiu LI ; Bin MING ; Zeng ZHANG ; Quanbo ZHANG ; Yufeng QING
Chinese Journal of Rheumatology 2024;28(9):640-647
Objective:To investigate the expression of N6-methyladenosine(m6A) modification-related genes and their possible roles in peripheral blood mononuclear cells (PBMCs) of patients with primary gouty arthritis (GA).Methods:Forty-five patients each with acute gout (AG), intermittent gout (IG), and age-and gender-matched healthy controls (HC) were collected from the outpatient clinic of the Department of Rheumatology and Immunology of the Affiliated Hospital of Chuanbei Medical College between October and December of 2023. The expression levels of m6A modification-related genes (METTL3、METTL14、WTAP、FTO、ALKBH5、IGF2BP2、IGF2BP3、YTHDF1、YTHDC2) in PBMCs among the 3 groups were detected by RT-qPCR and correlation analysis with clinical indicators was performed. Measurements conforming to normal distribution were analyzed using ANOVA or t-tests, and data were analyzed using the Kruskal-Wallis H-test and Mann-Whitney U-test for data that is not-normaly distributed. The value of m6A modification-related genes for the diagnosis of GA was evaluated using subject characterization curve ROC. Results:①There were statistically significant differences in the expression of IGF2BP2 ( Z=-3.59, P<0.001)、WTAP ( Z=-5.25, P<0.001)、METTL14 ( Z=-3.62, P<0.001)、YTHDF1 ( Z=-2.12, P=0.034)and YTHDC2 ( Z=-2.00, P=0.045) in the disease group and the normal control group. Among them, the expression of IGF2BP2 in the GA group [28.08 (17.99, 47.06)×10 -4] was significantly higher than that in the HC group [19.23 (12.90, 25.78)×10 -4], and the expressions of WTAP、METTL14、YTHDF1 and YTHDC2 in the GA group [298.61 (213.61, 377.80)×10 -4, 9.94 (6.43, 13.46)×10 -4, 52.63 (28.22, 72.77)×10 -4, 40.24 (20.74, 73.32)×10 -4] were significantly lower than those in the HC group [398.45(339.88, 454.89)×10 -4, 13.27(11.07, 15.85)×10 -4, 64.43(43.61, 87.10)×10 -4, 53.11(36.37, 79.28)×10 -4]. Further subgroup analysis revealed statistically significant differences in the expression of IGF2BP2、WTAP、METTL14、YTHDF1 and YTHDC2 among the 3 groups ( H=19.62、31.73、13.14、16.64、28.90, all P≤0.001). The expressions of WTAP and METTL14 in the AG group [311.13(234.96, 426.67)×10 -4, Z=-3.27, P=0.001; 9.64 (5.21, 15.21)×10 -4, Z=-2.71, P=0.008] and IG group [272.27 (203.29, 347.95)×10 -4, Z=-5.78, P<0.001; 10.40(6.88, 12.88)×10 -4, Z=-3.54, P=0.003] were lower than those in the HC group [398.45 (339.88, 454.89)×10 -4, 13.27(11.07, 15.85)×10 -4]. However, there was no significant difference between AG and IG group ( P>0.05). Both YTHDF1 and YTHDC2 were significantly lower in the AG group [38.10(16.19, 56.78)×10 -4, 24.31 (14.35, 42.77)×10 -4] than those in the IG group [64.13 (48.28, 74.40)×10 -4(Z=-3.54, P<0.001, 65.49 (39.89, 91.23)×10 -4(Z=-4.96, P<0.001)] and HC group [64.43 (43.61, 86.92)×10 -4(Z=-3.51, P<0.001), 53.11 (36.37, 79.28)×10 -4(Z=-4.25, P<0.001)]. But there was no statistically significant difference between IG and HC groups ( P>0.05); IGF2BP2 was significantly lower in the AG group [25.32(16.40, 40.43)×10 -4, Z=-2.46, P=0.014] and HC group [19.23 (12.90, 25.78)×10 -4, Z=-4.54, P<0.001] than in the IG group [31.10(22.60, 49.58)×10 -4], but the comparison between AG and HC showed no statistically significant difference( P>0.05). ②Spearman correlation analysis showed that in GA patients, the expression of IGF2BP2、METTL14 and YTHDF1 was positively correlated with plasma glucose、blood uric acid(sUA) and total cholesterol level respectively ( r=0.22, P=0.037; r=0.38, P=0.003; r=0.23, P=0.034), and WTAP was negatively correlated with GLU ( r=-0.25, P=0.020). ③The ROC curve for the joint prediction of the five differential genes showed that the 95% CI for area under the curve in GA was 0.90 (0.84, 0.95). Conclusion:The m6A modification-related genes are abnormally expressed in GA and are correlated with clinical indicators such as GLU and UA, which are hypothesized to be involved in the pathogenesis of GA and have a certain reference value for the evaluation of metabolism in GA patients.
10.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.

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