1.Downregulation of LINC00638 contributes to the pathogenesis of rheumatoid arthritis-associated interstitial lung disease via inhibiting the Nrf2/ARE signaling pathway
Zhuojun LIAO ; Naiwang TANG ; Jiahui CHEN ; Xueying SUN ; Jiamin LU ; Qin WU ; Ronghuan YU ; Ying ZHOU
Chinese Journal of Clinical Medicine 2025;32(3):421-431
Objective To identify long non-coding RNA (lncRNA) associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and investigate their mechanisms. Methods Peripheral blood samples were collected from RA-ILD patients (n=3), RA patients without lung involvement (n=3), and healthy controls (n=3). Next-generation sequencing was performed to screen differentially expressed lncRNA. A human fibrotic lung cell model was established by inducing the MRC-5 cell line with transforming growth factor-β (TGF-β). Following siRNA-mediated knockdown of target genes, changes in inflammatory and oxidative stress-related genes were analyzed via real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blotting and dual-luciferase reporter (DLR) assays were used to validate protein expression, ubiquitination levels, and nuclear translocation of oxidative stress regulators, and antioxidant response element (ARE) transcriptional activity. Rescue experiments were conducted to confirm the role of target lncRNA in oxidative stress and inflammation in fibrotic lung cells. Results High-throughput sequencing revealed significant downregulation of LINC00638 in RA-ILD patients. Knockdown of LINC00638 markedly reduced transcriptional levels of interleukin (IL)-4, nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and superoxide dismutase 2 (SOD2), while increasing IL-6, IL-1β, interferon-γ (IFN-γ), and reactive oxygen species (ROS) levels. Furthermore, LINC00638 knockdown decreased Nrf2 protein expression, increased its ubiquitination, reduced nuclear translocation, and suppressed ARE transcriptional activity. In MRC-5 cells, LINC00638 knockdown combined with N-acetylcysteine treatment restored Nrf2 and HO-1 levels while reducing IL-6 expression. Conclusions LINC00638 suppresses inflammatory responses in RA-ILD by activating the Nrf2/ARE antioxidant signaling pathway, suggesting its potential as a therapeutic target for diagnosis and treatment.
2.Pelvic exenteration for late complications of radiation-induced pelvic injury: a preliminary study
Yanjiong HE ; Zuolin ZHOU ; Qiyuan QIN ; Binjie HUANG ; Xiaoyan HUANG ; Jiamin LI ; Miaomiao ZHU ; Bing YAO ; Dejuan WANG ; Jianguang QIU ; Hui WANG ; Tenghui MA
Chinese Journal of Gastrointestinal Surgery 2023;26(10):940-946
Objective:To investigate the safety and efficacy of total pelvic exenteration (TPE) for treating late complications of radiation-induced pelvic injury.Methods:This was a descriptive case series study. The inclusion criteria were as follows: (1) confirmed radiation-induced pelvic injury after radiotherapy for pelvic malignancies; (2) late complications of radiation-induced pelvic injury, such as bleeding, perforation, fistula, and obstruction, involving multiple pelvic organs; (3) TPE recommended by a multidisciplinary team; (4) patient in good preoperative condition and considered fit enough to tolerate TPE; and (5) patient extremely willing to undergo the procedure and accept the associated risks. The exclusion criteria were as follows: (1) preoperative or intraoperative diagnosis of tumor recurrence or metastasis; (2) had only undergone diversion or bypass surgery after laparoscopic exploration; and (3) incomplete medical records. Clinical and follow-up data of patients who had undergone TPE for late complications of radiation-induced pelvic injury between March 2020 and September 2022 at the Sixth Affiliated Hospital of Sun Yat-sen University were analyzed. Perioperative recovery, postoperative complications, perioperative deaths, and quality of life 1 year postoperatively were recorded.Results:The study cohort comprised 14 women, nine of whom had recto-vagino-vesical fistulas, two vesicovaginal fistulas, one ileo-vesical fistula and rectal necrosis, one ileo-vesical and rectovaginal fistulas, and one rectal ulcer and bilateral ureteral stenosis. The mean duration of surgery was 592.1±167.6 minutes and the median blood loss 550 (100–6000) mL. Ten patients underwent intestinal reconstruction, and four the Hartmann procedure. Ten patients underwent urinary reconstruction using Bricker's procedure and 7 underwent pelvic floor reconstruction. The mean postoperative hospital stay was 23.6±14.9 days. Seven patients (7/14) had serious postoperative complications (Clavien-Dindo IIIa to IVb), including surgical site infections in eight, abdominopelvic abscesses in five, pulmonary infections in five, intestinal obstruction in four, and urinary leakage in two. Empty pelvis syndrome (EPS) was diagnosed in five patients, none of whom had undergone pelvic floor reconstruction. Five of the seven patients who had not undergone pelvic floor reconstruction developed EPS, compared with none of those who had undergone pelvic floor reconstruction. One patient with EPS underwent reoperation because of a pelvic abscess, pelvic hemorrhage, and intestinal obstruction. There were no perioperative deaths. During 18.9±10.1 months of follow-up, three patients died, two of renal failure, which was a preoperative comorbidity, and one of COVID-19. The remaining patients had gradual and significant relief of symptoms during follow-up. QLQ-C30 assessment of postoperative quality of life showed gradual improvement in all functional domains and general health at 1, 3, and 6 months postoperatively (all P<0.05). Conclusions:TPE is a feasible procedure for treating late complications of radiation-induced pelvic injury combined with complex pelvic fistulas. TPE is effective in alleviating symptoms and improving quality of life. However, the indications for this procedure should be strictly controlled and the surgery carried out only by experienced surgeons.
3.Pelvic exenteration for late complications of radiation-induced pelvic injury: a preliminary study
Yanjiong HE ; Zuolin ZHOU ; Qiyuan QIN ; Binjie HUANG ; Xiaoyan HUANG ; Jiamin LI ; Miaomiao ZHU ; Bing YAO ; Dejuan WANG ; Jianguang QIU ; Hui WANG ; Tenghui MA
Chinese Journal of Gastrointestinal Surgery 2023;26(10):940-946
Objective:To investigate the safety and efficacy of total pelvic exenteration (TPE) for treating late complications of radiation-induced pelvic injury.Methods:This was a descriptive case series study. The inclusion criteria were as follows: (1) confirmed radiation-induced pelvic injury after radiotherapy for pelvic malignancies; (2) late complications of radiation-induced pelvic injury, such as bleeding, perforation, fistula, and obstruction, involving multiple pelvic organs; (3) TPE recommended by a multidisciplinary team; (4) patient in good preoperative condition and considered fit enough to tolerate TPE; and (5) patient extremely willing to undergo the procedure and accept the associated risks. The exclusion criteria were as follows: (1) preoperative or intraoperative diagnosis of tumor recurrence or metastasis; (2) had only undergone diversion or bypass surgery after laparoscopic exploration; and (3) incomplete medical records. Clinical and follow-up data of patients who had undergone TPE for late complications of radiation-induced pelvic injury between March 2020 and September 2022 at the Sixth Affiliated Hospital of Sun Yat-sen University were analyzed. Perioperative recovery, postoperative complications, perioperative deaths, and quality of life 1 year postoperatively were recorded.Results:The study cohort comprised 14 women, nine of whom had recto-vagino-vesical fistulas, two vesicovaginal fistulas, one ileo-vesical fistula and rectal necrosis, one ileo-vesical and rectovaginal fistulas, and one rectal ulcer and bilateral ureteral stenosis. The mean duration of surgery was 592.1±167.6 minutes and the median blood loss 550 (100–6000) mL. Ten patients underwent intestinal reconstruction, and four the Hartmann procedure. Ten patients underwent urinary reconstruction using Bricker's procedure and 7 underwent pelvic floor reconstruction. The mean postoperative hospital stay was 23.6±14.9 days. Seven patients (7/14) had serious postoperative complications (Clavien-Dindo IIIa to IVb), including surgical site infections in eight, abdominopelvic abscesses in five, pulmonary infections in five, intestinal obstruction in four, and urinary leakage in two. Empty pelvis syndrome (EPS) was diagnosed in five patients, none of whom had undergone pelvic floor reconstruction. Five of the seven patients who had not undergone pelvic floor reconstruction developed EPS, compared with none of those who had undergone pelvic floor reconstruction. One patient with EPS underwent reoperation because of a pelvic abscess, pelvic hemorrhage, and intestinal obstruction. There were no perioperative deaths. During 18.9±10.1 months of follow-up, three patients died, two of renal failure, which was a preoperative comorbidity, and one of COVID-19. The remaining patients had gradual and significant relief of symptoms during follow-up. QLQ-C30 assessment of postoperative quality of life showed gradual improvement in all functional domains and general health at 1, 3, and 6 months postoperatively (all P<0.05). Conclusions:TPE is a feasible procedure for treating late complications of radiation-induced pelvic injury combined with complex pelvic fistulas. TPE is effective in alleviating symptoms and improving quality of life. However, the indications for this procedure should be strictly controlled and the surgery carried out only by experienced surgeons.
4.β-Lactam antibiotics promoting aging and clearance of RBCs would deteriorate the DIIHA
Qixiu YANG ; Fengyong ZHAO ; Qin LI ; Jiamin ZHANG ; Zhonghui GUO ; Ying YANG ; Chen WANG ; Ziyan ZHU
Chinese Journal of Blood Transfusion 2022;35(9):904-907
【Objective】 To analyze the influence of β-lactam antibiotics on RBC aging and clearance by detecting various indicators of aging and clearance on RBCs, as well as the differences in phagocytosis for erythrocytes before and after drugs treated in vitro. 【Methods】 RBCs were treated by β-lactam antibiotics, including Penicillin, Cefepime, Cefoperazone and Ceftazidime, and the changing of phosphatidylserine (PS) and clearance related CD markers, including CD35, CD47, CD55 and CD59 on the surface of the RBCs, were detected by flow cytometry at 0h and 24h after drugs treatment. The proportion of acanthocytes by microscope also at 0h and 24h after drugs treatment was calculated. The phagocytosis of drug-treated RBC was detected by monocyte monolayer assay (MMA). Untreated RBCs were incubated in PBS by the same condition as a negative control.The influence of β-lactam antibiotics on RBC aging and clearance by all the results above was studied. 【Results】 Compare to the untreated RBCs, the drug treated RBCs showed a higher PS level on the cell surface. The results showed by percentage as following(0 h vs 24 h): Penicillin 9.42% vs 93.30%, Cefepime 3.88% vs 57.27%, Cefoperazone 4.71% vs 75.75% and Ceftazidime 3.05% vs 43.19%. The acanthocytes ratio was as following(0 h vs 24 h): Penicillin 7.33% vs 86%, Cefepime 2.67% vs 52.67%, Cefoperazone 3.33% vs 67.67% and Ceftazidime 3.33% vs 90.67%. On the opposite, the clearance related CD markers, showed an obviously lower level after drugs treated(0 h vs 24 h): CD35: Penicillin 7.36% vs 11.87%, Cefepime 0.14% vs 28.51%, Cefoperazone 11.85% vs 21.55% and Ceftazidime 7.63% vs 8.73%; CD47: Penicillin 1.22% vs 9.13%, Cefepime 1.80% vs 0.86%, Cefoperazone 0.08% vs 6.85% and Ceftazidime 1.54% vs 5.50%; CD55: Penicillin 14.46% vs 44.31%, Cefepime 17.27% vs 38.41%, Cefoperazone 19.28% vs 33.28% and Ceftazidime 14.62% vs 34.13%; CD59: Penicillin 4.71% vs 20.56%, Cefepime 4.03% vs 7.60%, Cefoperazone 5.91% vs 22.38% and Ceftazidime 5.93% vs 30.89%. Drug-treated RBCs attached more to monocytes than untreated RBCs. 【Conclusion】 The β-lactam antibiotics could induce the changing of PS and the clearance of related CD markers on surface of RBCs. They also could lead acanthocytes and make the RBCs more susceptible to phagocytosis by monocytes. The β-lactam antibiotics could promote the RBCs aging and clearance, which might deteriorate the DIIHA.
5.Preparation of human monoclonal anti-C cell line from peripheral blood B lymphocytes of D--donor
Zhonghui GUO ; Fengyong ZHAO ; Demei ZHANG ; Dong XIANG ; Jiamin ZHANG ; Ying YANG ; Qin LI ; Qixiu YANG ; Chen WANG ; Ziyan ZHU
Chinese Journal of Blood Transfusion 2022;35(4):400-404
【Objective】 To establish human hybridoma cell lines, secreting monoclonal antibody against antigens of Rh blood system, from a donor with rare D--phenotype. 【Methods】 Peripheral blood B lymphocytes of an O type female donor, lacking C/c/E/e antigens on her erythrocyte, were transformed with Epstein-Barr virus (EBVs). EBVs were harvested from the cultural supernatant of B95-8 cells. The transformed lymphoblastoid cell line (LCL) secreting antibodies to C antigens were picked up and then hybridized with the myeloma SHM-D33 using electric fusion technique. Hybridoma cells were selected by HATD-Ouabain(HOTD)(Hypoxantine, Aminopterin, Thymidine, 2-Deoxycytide, and Ouabain)culture medium, microplate antibody screening and limited dilution subcloning. The monoclonal antibody was assayed by serological test and was confirmed by flow cytometry (FCM). 【Results】 From the cultural supernatant of D--peripheral blood transformed B lymphocytes, 3A6-C6, which agglutinated with R
6.Value of serum IgA/C3 ratio in the diagnosis of IgA nephropathy and its correlation with the clinicopathological features.
Shuangshuang ZHU ; Yongqiang LI ; Shulu ZHOU ; Qingzhu WEI ; Kangping DENG ; Xiaohong WANG ; Bin LI ; Jianghuan LIU ; Xinyu LIU ; Ying ZHANG ; Xiaofei SHAO ; Aiqun LIU ; Bifang WU ; Zhihong ZHAO ; Xiaomeng XU ; Hanfei LIN ; Qin LIU ; Jiamin LI ; Honglei WANG ; Qin ZHOU ; Chaoya ZHU ; Daoyuan LV ; Yue XIA ; Hequn ZOU
Journal of Southern Medical University 2015;35(12):1683-1688
OBJECTIVETo investigate the value of serum IgA/C3 ratio in the diagnosis of IgA nephropathy and explore its relationship with the clinicopathological features of the patients.
METHODSSixty-six patients with IgA nephropathy, 111 with other glomerular diseases, and 40 healthy control subjects without kidney disease were tested for serum IgA and C3 levels using CRM470 adjusted standardized immune turbidimetric method, and the IgA/C3 ratio was calculated. According to Oxford and Lee's classification criteria, we analyzed the pathological grades of the renal biopsy samples from patients with IgA nephropathy. The ROC curve was used to assess the value of serum IgA and IgA/C3 ratio in predicting IgA nephropathy.
RESULTSPatients with IgA nephropathy had an elevated serum IgA/C3 ratio than those with other glomerular diseases and the control subjects, with an area under the ROC curve of 0.776. An elevated serum IgA/C3 ratio was not found to significantly correlate with the pathological grade of renal biopsy samples in patients with IgA nephropathy.
CONCLUSIONIn the absence of renal biopsy findings, serum IgA/C3 ratio can help in the diagnosis of IgA nephropathy.
Biopsy ; Case-Control Studies ; Complement C3 ; analysis ; Glomerulonephritis, IGA ; blood ; diagnosis ; Humans ; Immunoglobulin A ; blood ; Kidney ; pathology
7.Role of inflammation in the mechanism of the commorbidity of depression and pain
Jiamin QIN ; Yongjing LU ; Lun CAI
Journal of Medical Postgraduates 2015;(8):893-896
Comorbid depression and chronic pain are highly prevalent in individuals suffering from physical illness .Here, we critically examine that inflammation is the possible mechanism of comorbidity of pain and depression .These mechanisms include direct effects of cytokines on the neuronal environment or indirect effects via downregulation of G protein -coupled receptor kinase 2, activation of the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase that generates toxic kynurenine metabolites .We review the role of in-flammation in the mechanism of the commorbidity of depression and pain .
8.Value of serum IgA/C3 ratio in the diagnosis of IgA nephropathy and its correlation with the clinicopathological features
Shuangshuang ZHU ; Yongqiang LI ; Shulu ZHOU ; Qingzhu WEI ; Kangping DENG ; Xiaohong WANG ; Bin LI ; Jianghuan LIU ; Xinyu LIU ; Ying ZHANG ; Xiaofei SHAO ; Aiqun LIU ; Bifang WU ; Zhihong ZHAO ; Xiaomeng XU ; Hanfei LIN ; Qin LIU ; Jiamin LI ; Honglei WANG ; Qin ZHOU ; Chaoya ZHU ; Daoyuan L ; Yue XIA ; Hequn ZOU
Journal of Southern Medical University 2015;(12):1683-1688
Objective To investigate the value of serum IgA/C3 ratio in the diagnosis of IgA nephropathy and explore its relationship with the clinicopathological features of the patients. Methods Sixty-six patients with IgA nephropathy, 111 with other glomerular diseases, and 40 healthy control subjects without kidney disease were tested for serum IgA and C3 levels using CRM470 adjusted standardized immune turbidimetric method, and the IgA/C3 ratio was calculated. According to Oxford and Lee's classification criteria, we analyzed the pathological grades of the renal biopsy samples from patients with IgA nephropathy. The ROC curve was used to assess the value of serum IgA and IgA/C3 ratio in predicting IgA nephropathy. Results Patients with IgA nephropathy had an elevated serum IgA/C3 ratio than those with other glomerular diseases and the control subjects, with an area under the ROC curve of 0.776. An elevated serum IgA/C3 ratio was not found to significantly correlate with the pathological grade of renal biopsy samples in patients with IgA nephropathy. Conclusion In the absence of renal biopsy findings, serum IgA/C3 ratio can help in the diagnosis of IgA nephropathy.
9.Value of serum IgA/C3 ratio in the diagnosis of IgA nephropathy and its correlation with the clinicopathological features
Shuangshuang ZHU ; Yongqiang LI ; Shulu ZHOU ; Qingzhu WEI ; Kangping DENG ; Xiaohong WANG ; Bin LI ; Jianghuan LIU ; Xinyu LIU ; Ying ZHANG ; Xiaofei SHAO ; Aiqun LIU ; Bifang WU ; Zhihong ZHAO ; Xiaomeng XU ; Hanfei LIN ; Qin LIU ; Jiamin LI ; Honglei WANG ; Qin ZHOU ; Chaoya ZHU ; Daoyuan L ; Yue XIA ; Hequn ZOU
Journal of Southern Medical University 2015;(12):1683-1688
Objective To investigate the value of serum IgA/C3 ratio in the diagnosis of IgA nephropathy and explore its relationship with the clinicopathological features of the patients. Methods Sixty-six patients with IgA nephropathy, 111 with other glomerular diseases, and 40 healthy control subjects without kidney disease were tested for serum IgA and C3 levels using CRM470 adjusted standardized immune turbidimetric method, and the IgA/C3 ratio was calculated. According to Oxford and Lee's classification criteria, we analyzed the pathological grades of the renal biopsy samples from patients with IgA nephropathy. The ROC curve was used to assess the value of serum IgA and IgA/C3 ratio in predicting IgA nephropathy. Results Patients with IgA nephropathy had an elevated serum IgA/C3 ratio than those with other glomerular diseases and the control subjects, with an area under the ROC curve of 0.776. An elevated serum IgA/C3 ratio was not found to significantly correlate with the pathological grade of renal biopsy samples in patients with IgA nephropathy. Conclusion In the absence of renal biopsy findings, serum IgA/C3 ratio can help in the diagnosis of IgA nephropathy.
10.Analysis of relationship between subfoveal choroidal thickness and refraction
Yangtao, XU ; Quan, LIU ; Sihe, DU ; Jiamin, QIN ; Xing, LIU ; Danyang, WANG ; Manli, LIU
Chinese Journal of Experimental Ophthalmology 2014;32(6):546-550
Background Choroidal thickness is closely associated with ametropia,and to study the influence of subfoveal choroidal thickness (SFCT) on refraction is very important for understanding the mechanism of refractive error more clearly.Objective This study was to investigate the relationship between SFCT and refraction.Methods A retrospective serial cases analysis was performed.Forty anisometrope patients were recruited in Zhongshan Ophthalmic Center from June 2012 to August 2012.The subjects were divided into 6-13 years group and 14-21 years group.Vision acuity was tested by the EDTRS visual acuity chart and ocular anterior segment was examined under the slit lamp microscope,and the fundus examination was performed by direct ophthalmoscope.Subjective and objective optometry was performed after pupils were dilated.EDI OCT was used to illuminate choroidal image.Ocular axial length (AL) was obtained by Lenstar 900.The difference in SFCT between myopic eyes and hyperopic eyes was compared using Student t test,and the correlations between SFCT and refraction were analyzed by Pearson linear analysis and linear regression analysis.Results The average SFCT was (307.82±88.47) μm in all the tested eyes,and the SFCT of myopic eyes and hyperopic eyes was (270.60±70.57) μm and (376.95±76.59) μm,respectively,with a significant difference between them (P =0.000).In the 6-13 years group,positive correlations were found between SFCT and diopters with the regression coefficient 18.60 and regression equation Y =18.60X +310.79 (r=0.345,F=21.110,P=0.000) as well as between SFCT and AL with the regression coefficient -31.76 and regression equation Y =-31.76X+1 039.97 (r=0.262,F=17.320,P=0.000).In the 14-21 years group,SFCT showed positive correlation with diopters,with the regression coefficient 23.38 and regression equation Y=23.38X+353.17 (r =0.430,F =27.210,P =0.000) and negative correlation with AL,with the regression coefficient-35.82 and regression equation Y =-35.82X+1 132.75 (r=0.237,F=15.650,P=0.000).Conclusions SFCT seems to be positive correlated with diopter.When the diopter shifts toward positive value,SFCT value increases,and whenever diopter increases-1 D,SFCT decreases 20 μm approximately.SFCT decreases with the increase of AL.

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