1.Research on the mechanism of leptin regulating core binding factor β to promote chondrocyte apoptosis
Jiafei YANG ; Zhujun ZHOU ; Guangdi LI ; Yuan HUANG ; Mi ZHANG ; Lianghong DONG
Chinese Journal of Orthopaedics 2025;45(7):436-445
Objective:To investigate the regulatory effect of leptin via the JAK2/STAT3 pathway on the core-binding factor β-subunit (CBFβ) and its molecular mechanism in promoting chondrocyte apoptosis.Methods:A total of five patients undergoing total knee arthroplasty due to knee osteoarthritis (OA group) and five patients undergoing amputation due to trauma (amputation group) were enrolled, and knee cartilage samples were obtained intraoperatively. Western blotting was used to detect the protein expression levels of leptin, CBFβ, matrix metalloproteinase-1 (MMP1), and MMP13. Flow cytometry was performed to determine the optimal treatment duration and concentration of leptin. Chondrocytes were divided into the following groups based on treatment conditions: control group (untreated chondrocytes), leptin group (chondrocytes treated with 50 ng/ml leptin), negative leptin group (chondrocytes transfected with a non-targeting sequence as a control), and leptin+shCBFβ group (chondrocytes transfected with shCBFβ to inhibit CBFβ expression). Apoptosis and the expression levels of MMP1 and MMP13 were analyzed in the four groups. Additionally, chondrocytes were categorized into the following groups for further analysis: control group (untreated cells), leptin group (cells stimulated with 50 ng/ml leptin for 48 h), AG490 group (cells treated with the JAK2/STAT3 inhibitor AG490), and leptin+AG490 group (cells pretreated with AG490 for 2 h followed by 50 ng/ml leptin stimulation for 48 h). The protein expression levels of CBFβ, MMP1, and MMP13, as well as the apoptosis rate, were examined in the four groups.Results:The relative expression levels of leptin, CBFβ, MMP1, and MMP13 in the amputation group were 0.66±0.06, 0.69±0.06, 0.74±0.05, and 0.41±0.03, respectively, which were significantly lower than those in the OA group (1.04±0.10, 1.06±0.09, 0.95±0.04, and 0.99±0.09, respectively) ( P<0.05). The optimal treatment duration and concentration of leptin were determined to be 48 h and 50 ng/ml, respectively. The expression levels of MMP1 and MMP13 significantly differed among the control, leptin, negative leptin, and leptin+shCBFβ groups ( P<0.05). Specifically, the leptin group showed higher expression levels compared to the control group, while the leptin+shCBFβ group exhibited lower expression levels than the leptin group ( P<0.05). The apoptosis rates of chondrocytes in the four groups were 4.55%±1.30%, 22.52%±2.03%, 22.03%±2.01%, and 5.15%±0.91%, respectively, with significant differences ( F=114.066, P<0.001). The apoptosis rate in the leptin group was significantly higher than that in the control group, while the leptin+shCBFβ group exhibited a significantly lower apoptosis rate than the leptin group ( P<0.05). Similarly, significant differences were observed in the expression levels of CBFβ, MMP1, and MMP13 among the control, leptin, AG490, and leptin+AG490 groups ( P<0.05). The expression levels in the leptin group were higher than those in the control group, while the leptin+AG490 group exhibited lower expression levels compared to the leptin group ( P<0.05). The apoptosis rates of chondrocytes in the control, leptin, AG490, and leptin+AG490 groups were 5.19±0.94%, 31.52±2.63%, 5.51±1.41%, and 10.47±0.85%, respectively, with significant differences ( F=117.104, P<0.001). The apoptosis rate in the leptin group was significantly higher than that in the control group, while the leptin+AG490 group exhibited a significantly lower apoptosis rate than the leptin group ( P<0.05). Conclusion:Leptin promotes CBFβ expression via the JAK2/STAT3 pathway, leading to chondrocyte apoptosis and extracellular matrix degradation.
2.Research on the mechanism of leptin regulating core binding factor β to promote chondrocyte apoptosis
Jiafei YANG ; Zhujun ZHOU ; Guangdi LI ; Yuan HUANG ; Mi ZHANG ; Lianghong DONG
Chinese Journal of Orthopaedics 2025;45(7):436-445
Objective:To investigate the regulatory effect of leptin via the JAK2/STAT3 pathway on the core-binding factor β-subunit (CBFβ) and its molecular mechanism in promoting chondrocyte apoptosis.Methods:A total of five patients undergoing total knee arthroplasty due to knee osteoarthritis (OA group) and five patients undergoing amputation due to trauma (amputation group) were enrolled, and knee cartilage samples were obtained intraoperatively. Western blotting was used to detect the protein expression levels of leptin, CBFβ, matrix metalloproteinase-1 (MMP1), and MMP13. Flow cytometry was performed to determine the optimal treatment duration and concentration of leptin. Chondrocytes were divided into the following groups based on treatment conditions: control group (untreated chondrocytes), leptin group (chondrocytes treated with 50 ng/ml leptin), negative leptin group (chondrocytes transfected with a non-targeting sequence as a control), and leptin+shCBFβ group (chondrocytes transfected with shCBFβ to inhibit CBFβ expression). Apoptosis and the expression levels of MMP1 and MMP13 were analyzed in the four groups. Additionally, chondrocytes were categorized into the following groups for further analysis: control group (untreated cells), leptin group (cells stimulated with 50 ng/ml leptin for 48 h), AG490 group (cells treated with the JAK2/STAT3 inhibitor AG490), and leptin+AG490 group (cells pretreated with AG490 for 2 h followed by 50 ng/ml leptin stimulation for 48 h). The protein expression levels of CBFβ, MMP1, and MMP13, as well as the apoptosis rate, were examined in the four groups.Results:The relative expression levels of leptin, CBFβ, MMP1, and MMP13 in the amputation group were 0.66±0.06, 0.69±0.06, 0.74±0.05, and 0.41±0.03, respectively, which were significantly lower than those in the OA group (1.04±0.10, 1.06±0.09, 0.95±0.04, and 0.99±0.09, respectively) ( P<0.05). The optimal treatment duration and concentration of leptin were determined to be 48 h and 50 ng/ml, respectively. The expression levels of MMP1 and MMP13 significantly differed among the control, leptin, negative leptin, and leptin+shCBFβ groups ( P<0.05). Specifically, the leptin group showed higher expression levels compared to the control group, while the leptin+shCBFβ group exhibited lower expression levels than the leptin group ( P<0.05). The apoptosis rates of chondrocytes in the four groups were 4.55%±1.30%, 22.52%±2.03%, 22.03%±2.01%, and 5.15%±0.91%, respectively, with significant differences ( F=114.066, P<0.001). The apoptosis rate in the leptin group was significantly higher than that in the control group, while the leptin+shCBFβ group exhibited a significantly lower apoptosis rate than the leptin group ( P<0.05). Similarly, significant differences were observed in the expression levels of CBFβ, MMP1, and MMP13 among the control, leptin, AG490, and leptin+AG490 groups ( P<0.05). The expression levels in the leptin group were higher than those in the control group, while the leptin+AG490 group exhibited lower expression levels compared to the leptin group ( P<0.05). The apoptosis rates of chondrocytes in the control, leptin, AG490, and leptin+AG490 groups were 5.19±0.94%, 31.52±2.63%, 5.51±1.41%, and 10.47±0.85%, respectively, with significant differences ( F=117.104, P<0.001). The apoptosis rate in the leptin group was significantly higher than that in the control group, while the leptin+AG490 group exhibited a significantly lower apoptosis rate than the leptin group ( P<0.05). Conclusion:Leptin promotes CBFβ expression via the JAK2/STAT3 pathway, leading to chondrocyte apoptosis and extracellular matrix degradation.
3.A Meta-analysis on the infection rates on Mycoplasma genitalium in the genitourinary tract of different populations in China
Yan XUAN ; Lanxin WEI ; Xiang HONG ; Xiaoyue ZHU ; Shuheng DONG ; Qinyu YAN ; Lianghong WANG ; Bei WANG
Chinese Journal of Epidemiology 2021;42(2):335-342
Objective:Mycoplasma genitalium (Mg) is an opportunity pathogenic microorganism mainly transmitted through sexual contact. In recent years, scholars have paid more attention to Mg infection and pathogenicity. This study was aimed to understand the condition of Mg in the genitourinary tract of different populations in China and provide evidence for further study of its pathogenic characteristics. Methods:Cross-section studies of Mg infection in the Chinese community were searched by China National Knowledge Infrastructure (CNKI), Wanfang digital database, SinoMed, Pubmed, and Web of Science from database construction to March 10 th, 2020. Studies were sifted and screened independently by two evaluators based on inclusion and exclusion criteria, and Meta-analysis was conducted with R 1.1.463. If I 2≤50%, the fixed-effect model should be adopted, if I 2>50%, the random effect model should be adopted, and through subgroup analysis, the source of heterogeneity should be found out as far as possible. Results:A total of 47 research articles were included in this article, all of which were medium and high-quality articles. There was no obvious publication bias, and the results were more reliable. The research contained 19 provinces and Hong Kong Special administrative region, including 519 healthy people, 10 504 patients from clinics or hospitals of sexual transmitted disease (STD), 3 200 on Gynecology and 1 624 on Urology, 1 082 patients with men who have sex with men(MSM), 1 842 patients with Female sex worker(FSW), and 3 691 patients with HIV/AIDS. The infection rate of Mg in the genitourinary tract of the healthy population was 0.94% (95% CI: 0.07%-2.78%), the infection rate of Mg was 11.58% (95% CI: 8.57%-14.97%), 15.22% (95% CI: 7.99%-24.27%), 7.32% (95% CI: 4.24%-11.16%) among patients from clinics or hospitals of STD, gynecology and urology respectively. The infection rate of MSM was 9.70% (95% CI: 3.06%-19.52%),the infection rate of FSW was 13.49% (95% CI: 11.97%-15.08%). The infection rate of Mg among HIV infected patients was 20.46% (95% CI: 13.67%-28.22%). Conclusions:The infection rate of Mg in a healthy population was low. Mg infection rate in the genitourinary tract of other groups was still higher, which is worthy of further attention.
4.Clinicopathologic features and prednisone therapeutic effect of 50 cases of proliferative sclerosing IgA nephropathy
Mingming MA ; Baozhang GUAN ; Lihua LUO ; Bo HU ; Xiangnan DONG ; Lianghong YIN
Chinese Journal of Nephrology 2016;32(8):568-572
Objeetive To analyze the clinicopathologic features of proliferative sclerosing IgA nephropathy and the efficacy of prednisone therapy.Methods A retrospective analysis was conducted,enrolling 50 patients with biopsy-proven primary proliferative sclerosing IgA nephropathy who were admitted in the Hospital from January 2005 to June 2015-26 males and 24 females,mean age (36.8 ± 10.4) years.Clinicopathologic features and prednisone therapeutic effect were analyzed.Results The clinical manifestations of 50 cases were nephritis syndrome with varying degrees of renal insufficiency,including 32 cases (64.0%) with hypertension,15 cases (30.0%) with microscopic hematuria.Renal biopsy showed the incidence of glomerular global sclerosis was 17.0%-47.2%,tubular atrophy/ interstitial fibrosis outstanding (T0 50%,T1 32%,T2 18%).After prednisone treatment,compared with sustained remission group and relapse group,invalid patients had higher incidence of hypertension (P < 0.05),relatively lower Hb (P < 0.01) and serum albumin,more significant renal dysfunction (P < 0.01),more severe glomerular global sclerosis,segmental sclerosis,tubular atrophy/ interstitial fibrosis,while the lower interstitial inflammatory cell infiltration.During the follow-up,which lasted from 6 to 132 months (median 27.3 months),the effective rate of treatment was 74.0% after sufficient prednisone or half dose prednisone therapy.Repeated recurrence rate was 32.0%.At the end of the follow-up period,13(26.0%) patients entered the stage of uremia.Conclusions Application of glucocorticoids in the treatment of proliferative sclerosing IgA nephropathy can protect renal function and delay the progression of renal impairment.The efficacy of glucocorticoids therapy is significantly associated with the presence or absence of hypertension,the degree of renal function impairment,and the severity of the onset of renal pathology.
5.A Case Report of Acute Arterial Embolization of Right Lower Extremity As the Initial Presentation of Nephrotic Syndrome with Minimal Changes.
Mingming MA ; Lihua LUO ; Shufei ZENG ; Xiaoyi CHEN ; Fanna LIU ; Baozhang GUAN ; Zhanhua CHEN ; Xiangnan DONG ; Lianghong YIN
Chinese Medical Sciences Journal 2016;31(4):261-263
Acute Disease
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Adult
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Humans
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Iliac Artery
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Lower Extremity
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blood supply
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Male
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Nephrotic Syndrome
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complications
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Thrombosis
;
etiology
6.Relationship between serum AECA and clinical signatures of ANCA negative pauci-immune deposition type crescentic glomerulonephritis patients
Xiangnan DONG ; Rui CAO ; Lianghong YIN
Chinese Journal of Immunology 2016;32(6):875-877,881
Objective:To investigate the expression of anti-endothelial cell antibodies(AECA) in patients serum with anti-neutrophil cytoplasmic antibody( ANCA) negative pauci-immune deposition type crescentic glomerulonephritis and its relationship with clinical signatures. Methods:We selected 94 pauci-immune deposition type crescentic glomerulonephritis patients from 2010 to 2015 treated in our hospital,45 of which with ANCA-negative( observation group) and 49 cases of ANCA-positive patients ( control group) , AECA levels of each groups serum were detected by Western blot test. Results: The average age of the observation group and Bermingham vasculitis activity score(BVAS) respectively (41. 08 +9. 43) years old and (15. 03 +3. 82),significantly lower than the control group (P<0. 05);the observation group had fever,joint pain accounted for 26. 67% and 13. 33%,significantly lower than the control group ( P<0. 05 );the observation group of nephrotic syndrome accounted for 48. 89%, higher than the control group ( P<0. 05);observation group positive rate of serum AECA was 46. 67%,significantly lower than the control group 81. 63% (P<0. 05);the observation group IgG-AECA identified 7 proteins,while the control group had identified 11 proteins,of which the observation group the positive rate of anti 90 kD antibody was 13. 33%( 6/45 ) , significantly lower than the control group 51. 02%( 25/49 ) ( P<0. 05 );observation group of anti 76 kD antibody positive patients had rash ratio of 100%, significantly higher than negative patients ( P<0. 05),anti 200 kD antibody positive the BVAS score of the patients was (18. 02 + 2. 51),which was significantly higher than that of the negative patients ( P < 0. 05 ) . Conclusion: The different level of AECA in ANCA negative pauci-immune crescentic glomerulonephritis patients may be associated with certain clinical manifestations;clinical manifestations differences between the ANCA negative and positive patients may be associated with different expression of the AECA related,the detail need a further study.

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