1.Clinical features of 40 cases of anti-Ku antibody associated disease
Qihua YANG ; Xin ZHANG ; Kunlong LYU ; Lei ZHANG ; Yujie HE ; Shengyun LIU
Chinese Journal of Rheumatology 2021;25(6):378-382,c6-1
Objective:By analyzing the clinical characteristics of anti-Ku antibody associated disease, this paper aims to improve the diagnosis and treatment level of it.Methods:The clinical symptoms, laboratory tests and prognosis of 40 anti-Ku-antibody positive patients from the First Affiliated Hospital of Zhengzhou University from September 2017 to September 2019 were retrospectively collected, and then hierarchical clustering analyzed.Results:The average age of 40 anti-Ku positive patients was 48±18 years, and the male to female ratio was 1∶4. The average follow-up was (11±7) months, of which 2 cases were accompanied by malignant tumors and 3 cases died. Interstitial lung disease was most common and was found in 24 cases (60%). The most common disease was inflammatory myopathy (11 cases, 28%), followed by systemic lupus erythematosus (SLE) (9 cases, 22%). According to hierarchical cluster analysis, the anti-Ku-antibodies positive patients were divided into 3 groups. Among them, group A had the highest incidence of pulmonary interstitial fibrosis (84%, P<0.01), and the lowest incidence of renal involvement (0, P<0.01), cytopenia (0, P<0.01), serositis (0, P<0.01). Although the incidence of anti-Jo-1 antibody positivity in group A was the highest (16%, P=0.44) but without statistically significant difference. The characters of group A were in line with inflammatory myopathy. Group C had the highest incidence of renal involvement (57%), lupus rash (71%), cytopenia (57%), low complement (71%) and lupus-related antibodies positivity ( P value were all<0.05), which was in line with SLE. These two groups had their own significant biological characteristics, and were rarely overlapped. Conclusion:Anti-Ku antibody appears in a wide spectrum of autoimmune diseases, among which inflammatory myopathy is the most common, followed by SLE. Patients with anti-Ku antibody rarely have SLE and myositis overlapped, and the overall prognosis is good, but it is necessary to be alert to complications, such as tumors.
2.Effect and mechanism of microRNA-24 on cell proliferation and migration of osteosarcoma cell line U2OS
Journal of International Oncology 2017;44(7):490-495
Objective To investigate the effect of microRNA-24 (miR-24) on cell proliferation and migration in osteosarcoma cell line U2OS and its possible mechanism.Methods U2OS cell line with miR-24 over-expression was established by transfecting miR-24 mimic, and then cell proliferation and migration in control group, negative control group and miR-24 over-expression group were detected with real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assay, cell counting kit-8 (CCK-8) assay and Transwell assay, respectively.Epithelial-mesenchymal transition (EMT) progression and activation of nuclear factor-κB (NF-κB) pathway were detected by Western blotting.Results The expressions of miR-24 in the control group, negative control group and miR-24 over-expression group were 1.00±0.00, 1.03±0.08 and 2.46±0.29, with significant difference (F=11.026, P=0.012).Compared with the control group, the expression of miR-24 in human osteosarcoma U2OS cell line was significantly increased after transfecting miR-24 mimic (t=4.604, P=0.009).After over-expression of miR-24 for 24 h, 48 h and 72 h, U2OS cell viabilities were decreased significantly compared with the control group [(3.56±0.27)% vs.(8.63±0.79)%, t=3.896, P=0.016;(20.16±1.09)% vs.(54.77±5.42)%, t=4.813, P=0.008;(45.47±3.16)% vs.(95.52±8.56)%, t=7.173, P=0.002)].After over-expression of miR-24 for 24 h, the cell migration rates in control group, negative control group and miR-24 over-expression group were (100.00±0.00)%, (99.26±5.85)% and (31.37±2.09)%, respectively, and there was statistically significant difference among the three groups (F=12.175, P=0.009);and compared with control group, cell migration rate was decreased significantly after over-expression of miR-24 (t=3.843, P=0.004).Meanwhile, over-expression of miR-24 up-regulated the expression levels of epithelial cell markers E-cadherin (t=3.852, P=0.018) and β-catenin (t=3.512, P=0.024), while down-regulated the expression levels of mesenchymal cell markers N-cadherin (t=3.832, P=0.018) and vimentin (t=4.058, P=0.012), with a suppressed EMT progress.Other than that, miR-24 over-expression inhibited the expressions of NF-κB (p65) (t=4.813, P=0.008), phosphorylation inhibitor of nuclear factor kappa-B kinase α (p-IKK-α) (t=3.764, P=0.013) and phosphorylation inhibitor of nuclear factor kappa-B kinase complex α (p-IκB-α) (t=4.064, P=0.012), suppressing the activation of NF-κB pathway.Conclusion miR-24 can suppress cell proliferation and migration of osteosarcoma cell line U2OS in vitro, and its mechanism may be related to the suppression of NF-κB activation and EMT progression.It hints that miR-24 may be used as a potential new target for osteosarcoma therapy.
3.Preliminary research on effect of combination of Ajuga decumbens and Poriacocos on invasion and metastasis of breast cancer
Jingjing WANG ; Bo PENG ; Rong HE ; Qihua XU ; Jingya HAN ; Jianrong LI
Chinese Pharmacological Bulletin 2017;33(4):581-588
Aim To investigate the effect of Ajuga decumbens(HBG), Poria cocos(FL) and their combination on the metastasis of invasive breast cancer cells and the related mechanisms.Methods We conducted several assays including cell adhesion assay, scratch assay and transwell invasion assay.Western blot analysis was employed to detect the expression of associated proteins of EMT and MAPK signaling pathway.Results FL,HBG and their combination could significantly inhibit the adhesion, migration and invasion of MDA-MB-231 and SK-BR-3 cells.HBG and FL had markedly synergistic effect, and the best compatibility ratio was 10 ∶1.HBG, FL and their combination could reverse EMT of breast cancer cells, which increased the levels of epithelial biomarkers, such as β-catenin, E-cadherin and ZO-1, and reduced the levels of mesenchymal biomarkers, such as vimentin.Moreover, treatment of the cells with HBG, FL and their combination resulted in marked inhibition of phosphorylation of ERK1/2, JNK and p38.Conclusions The combination of HBG and FL have the ability to inhibit breast cancer cell invasion by targeting the expression of MAPK pathway as well as suppressing the epithelial-to-mesenchymal transition.
4.Clinical Effect of Ubenimex Capsules Combined with SOX Chemotherapy on Treatment of Advanced Gastric Cancer
Wei LI ; Zhongqiang YAO ; Zhongqiu LIU ; Qihua HE ; Xiaojing YU ; Zhigang FAN
Progress in Modern Biomedicine 2017;17(23):4495-4497,4470
Objective:To study the clinical effect and safety of ubenimex capsules and SOX chemotherapy on the advanced gastric cancer.Methods:90 patients with advanced gastric cancer who were treated in our hospital from September 2013 to September 2015 were selected and randomly divided into the observation group (n=45) and the control group (n=45).The patients in the control group were treated with SOX chemotherapy,while the patients in the observation group were treated with ubenimex capsules on the basis of control group.Then the serum levels of MMP-2 and MMP-9,the immune functions,the clinical efficacy,the adverse reactions and survival rate of two groups were observed and compared before and after the treatment.Results:After treatment,the CD4+,CD4+/CD8+ in the observation group were higher than those of the control group (P<0.05);The levels of MMP2 and MMP-9 in the observation group were lower than those of the control group (P<0.05);The total effective rate of the observation group was higher than that of the control group [68.89%(31/45) vs 48.89%(22/45)] (P<0.05);The incidence of thrombocytopenia,leukopenia,nausea and vomiting and abnormal liver functions in the observation group was lower than that of the control group (P<0.05);The survival rate of the observation group was higher than that of the control group at 6 months and 12 months [93.33% (42/45) vs 77.78% (35/45),82.22% (37/45) vs 57.78% (26/45)](P<0.05).Conclusion:Compared with SOX chemotherapy alone,ubenimex capsules and SOX chemotherapy could effectively improve the immune function,enhance the long-term survival rate with high safety of patients with advanced gastric cancer.
5.Propensity Score Matching Analysis of VATS Lobectomy and Sublobar Resection for Stage I Lung Adenocarcinoma
LIU YANG ; ZHONG SHENGYI ; HE QIHUA ; ZHANG JIANRONG ; CHEN XUEWEI ; GUO MINZHANG ; HE JIANXING
Chinese Journal of Lung Cancer 2017;20(1):47-54
Background and objective National Comprehensive Cancer Network (NCCN) guidelines recom-mend video-assisted thoracoscopic surgery (VATS) anatomical lobectomy as the ifrst choice for the treatment of resectable lung cancer. However, sublobar resection offers signiifcantly better functional preservation compared with lobectomy for stage I lung cancer. At present, the inferiority of sublobar resection to lobectomy is still uncertain. Herein, we compared the prognoses of these two types of surgical treatment for stage I lung adenocarcinoma. Methods Retrospective research was conducted on 258 patients with stage I lung adenocarcinomas who underwent VATS lobectomy and sublobar resection at the First Affliated Hospital of Guangzhou Medical University between January 2009 and December 2011. VATS lobectomy was performed on 222 patients, and VATS sublobe resection was performed on 36 patients. Propensity score matching analyses were conducted on the two groups. Results A total of 70 patients were matched in the two groups. No signiifcant difference was observed between the lobectomy and sublobar resection groups atfer matching (P=0.137). hTe disease-free survival (DFS) of the two groups were 49.3 and 42.7 months, and their overall survival (OS) were 50.3 and 49.0 months (P=0.122). Further, stratiifed analysis showed no signiifcant differences in DFS and OS between the two groups with stage Ia lung adenocarcinoma. Nev-ertheless, the DFS and OS of the two groups signiifcantly differed in matched patients with stage Ib lung adenocarcinomas. Conclusion Sublobar resection could achieve a similar prognosis to VATS lobectomy for stage Ia lung adenocarcinoma. Lo-bectomy should still be the ifrst choice for the treatment of stage Ib lung adenocarcinoma.
6.Effects of zhuhong ointment on mercury cumulation and renal organization modality in skin-impaired model rat.
Han LIN ; Xuhui ZHANG ; Jianxun DONG ; Jianrong LI ; Rong HE ; Bo PENG ; Qihua XU ; Leping WANG ; Ling LUO
China Journal of Chinese Materia Medica 2012;37(6):739-743
OBJECTIVETo study the effects of Zhuhong ointment on accumulation in the body of mercury and the pathological morphology changes of kidney, via the measurement of related indicators of the skin-impaired model rat.
METHODEighty-eight SD rats were randomly divided into the impairment control group, and high-, middle-, low-dose Zhuhong ointment groups. Each group was treated by corresponding methods for 4 weeks, and recovering for 4 weeks. Urinary potein (PRO), pH, Beta N-acetyl aminoglycosidase enzymes (NAG) and beta2-microglobulin (beta2-MG) contents in urine were taken as monitoring indexes, blood urea nitrogen (BUN) and serum creatinine (SCr) in blood and the levels of mercury in urine, blood and kidney were tested, and the pathological morphology changes of kidney were observed.
RESULTAfter treatment for 4 weeks, compared with impairment control group, the levels of mercury in urine, blood and kidney in every dose group increased significantly (P < 0.01). And the relation exists between toxicity and dose on Zhuhong ointment. After recovery for 4 weeks, the levels of mercury in urine and blood in every dose group restore normal, while the level of mercury in kidney in high- dose group still increased (P < 0.01). The level of NAG increased only in high-dose group. There was no significant difference in NAG contents between Zhuhong ointment groups and the impairment control group (P < 0.05).
CONCLUSIONExcess using Zhuhong ointment repeatedly may lead to accumulation of mercury and pathological morphology changes of kidney. So the levels of mercury in the body and related indicators of renal functions should be tested in clinical when long-term using Zhuhong ointment.
Acetylglucosaminidase ; drug effects ; urine ; Animals ; Blood Urea Nitrogen ; Creatinine ; blood ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; toxicity ; Female ; Hydrogen-Ion Concentration ; drug effects ; Kidney ; drug effects ; enzymology ; metabolism ; pathology ; Male ; Mercury ; blood ; metabolism ; urine ; Ointments ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Retinol-Binding Proteins ; drug effects ; urine ; Skin ; drug effects ; injuries ; Time Factors ; beta 2-Microglobulin ; urine
7.Effect of zhuhong ointment on renal antioxidant capability in skin ulcer model rats.
Leping WANG ; Jianrong LI ; Jianxun DONG ; Ling LUO ; Rong HE ; Bo PENG ; Qihua XU ; Han LIN ; Xuhui ZHANG
China Journal of Chinese Materia Medica 2012;37(6):735-738
OBJECTIVETo study the effect of repeated administration of Zhuhong ointment on renal antioxidant capability of ulcerous skin in rats, in order to further discuss the mechanism of mercury contained in Zhuhong ointment on the antioxidant capability of kidney in skin ulcer rats.
METHODEighty SD rats were randomly divided into eight groups: Zhuhong ointment A, B, C, D, E (1.219, 0.609, 0.305, 0.152, 0.76 g x kg(-1)) groups, the vaseline group, the ulcer model group and the impairment control group. The levels of NAG and RBP of toxicity for early kidney tubular injury and T-AOC, SOD, GSH-PX and GSH in kidney were determined after consecutive administration for 14 days.
RESULTCompared with ulcer model group, the levels of RBP in groups A, B, C and D increased, while the levels of NAG increased only in the group A. The level of T-AOC increased in groups A, B and C. The level of T-SOD increased in the group E, while it dropped down greatly in the group A. The level of GSH-PX increased in groups A, B and C. The content of GSH increased in every dose groups.
CONCLUSIONAntioxidant capacity in rats can be increased in a reasonable dose of Zhuhong ointment, but some antioxidant activity can be notably inhibited by with the increase of dose.
Acetylglucosaminidase ; drug effects ; urine ; Animals ; Antioxidants ; analysis ; metabolism ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; toxicity ; Glutathione ; drug effects ; metabolism ; Glutathione Peroxidase ; drug effects ; metabolism ; Kidney Tubules ; drug effects ; injuries ; metabolism ; Male ; Mercury ; metabolism ; Ointments ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Retinol-Binding Proteins ; drug effects ; urine ; Skin Ulcer ; metabolism ; microbiology ; Specific Pathogen-Free Organisms ; Staphylococcal Skin Infections ; metabolism ; Superoxide Dismutase ; drug effects ; metabolism ; Time Factors
8.Comparison of effects of badu shengji san on rats with different injured skins.
Yanli LU ; Rong HE ; Bo PENG ; Qihua XU ; Xuhui ZHANG ; Han LIN ; Jianrong LI
China Journal of Chinese Materia Medica 2012;37(6):711-714
OBJECTIVETo compare the effects of Badu Shengji San (BDSJS) on rats with different injured skins.
METHODThe injured and ulcerous skin rat model was established to observe the renal injury induced by BDSJS, a mercury-containing external preparation of Chinese medicine, with urinary N-acetyl-beta-D-glucosaminidase (NAG) and retinol binding protein (RBP) as indicators of renal toxicity.
RESULTCompared to injured skin rats with the same dose, both of high and low-dose ulcerous skin groups showed obvious increase in urinary RBP and kidney coefficients, significant pathomorphological changes in renal tubules and notable epithelial cytopathic effects. In terms of NAG, the high-dose ulcerous skin group saw no significant increase, but the low-dose group recorded sharp rise.
CONCLUSIONThe renal toxicity induced by BDSJS in ulcerous skin rats was more toxic than that in injured skin ones.
Acetylglucosaminidase ; urine ; Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; toxicity ; Epithelial Cells ; drug effects ; metabolism ; pathology ; Kidney Tubules ; drug effects ; metabolism ; pathology ; Male ; Mercury ; toxicity ; urine ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Retinol-Binding Proteins ; urine ; Skin ; drug effects ; injuries ; Skin Ulcer ; drug therapy ; microbiology ; Staphylococcal Skin Infections ; drug therapy
9.Comparative study on external use of mercury-containing preparation badu shengji san in sensitive monitoring indicators of induced early renal injury.
Yanli LU ; Rong HE ; Qihua XU ; Bo PENG ; Jianrong LI
China Journal of Chinese Materia Medica 2012;37(6):706-710
OBJECTIVETo compare the sensitivity of early renal injury induced by mercury-containing medicine in rats, including urinary N-acetyl-beta-D-glucosdminidase (NAG), beta2-microglobulin (beta2-MG), retinol binding protein (RBP) and clusterin (CLU).
METHODBadu Shengji San(BDSJS), a mercury-containing preparation of traditional Chinese medicine, was adopted as the mercury contact drug. The lowest effective toxic dose was used to observe its effect on serum creatinine (SCr), blood urea nitrogen (BUN), and such early renal injury indicators as NAG, RBP, beta2-MG and CLU and compare the sensitivity of tested indicators.
RESULTCompared to the broken skin group, groups with administration of 60 and 120 mg x kg(-1) doses of BDSJS showed no obvious difference in SCr and BUN when kidney indicators is remarkably increased and obvious pathological changes were found in kidney tubules but with significant increase in the urinary level of CLU and the levels of NAG and RBP. H&E staining of renal tubule showed that exposure of 30 mg x kg(-1) BDSJS had no significant morphological changes, but at the same concentrations, the level of RBP was markedly increased. Urinary beta2-MG levels were markedly decreased in BDSJS 30, 60 mg x kg(-1) group rats, whereas 120 mg x kg(-1) dose group showed no obvious change in urinary beta2-MG levels.
CONCLUSIONUrinary RBP, NAG and CLU were more sensitive than SCr and BUN as indicators for early renal injury in the order of RBP > NAG > CLU, and urinary RBP, NAG would increase earlier than beta2-MG.
Acetylglucosaminidase ; urine ; Animals ; Blood Urea Nitrogen ; Clusterin ; urine ; Creatinine ; blood ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; toxicity ; Epithelial Cells ; drug effects ; metabolism ; pathology ; Kidney Tubules ; drug effects ; metabolism ; pathology ; Male ; Mercury ; blood ; metabolism ; toxicity ; urine ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Retinol-Binding Proteins ; urine ; Skin ; drug effects ; injuries ; Time Factors ; beta 2-Microglobulin ; urine
10.Study on mercury accumulation in rats induced by badu shengji san.
Yanli LU ; Rong HE ; Bo PENG ; Qihua XU ; Xuhui ZHANG ; Han LIN ; Jianrong LI
China Journal of Chinese Materia Medica 2012;37(6):700-705
OBJECTIVETo study the mercury accumulation in injured skin rats induced by Badu Shengji San (BDSJS), a traditional Chinese medicine preparation for external use.
METHODInjured skin rats were treated with BDSJS for consecutively 4 weeks. During the 4 weeks and the following 4 weeks after the drug withdrawal, samples were collected for determining mercury contents in blood, urine and kidney, with urinary N-acetyl-beta-D-glucosaminidase(NAG) and beta2-microglobulin (beta2-MG) as indicators of renal toxicity and serum biochemical indicators of hepatic and renal functions. Additionally, activated partial thromboplastin time (APTT), prothrombin time (PT) and kidney and renal pathological changes were also observed.
RESULTCompared to injured skin rats, mercury contents of blood, urine and kidney were increased significantly in low, middle and high-dose BDSJS groups administered for consecutive 4 weeks. The levels of mercury showed decreases in urine (89%, 78%, 93%) and kidney (55%, 51%, 57%), and blood mercury concentration recovered to the normal range in low, middle and high-dose BDSJS groups after the drug withdrawal for 4 weeks. Kidney coefficient and beta2-MG were remarkably increased and renal tubular epithelial cell swelling could be found in the high-dose group, and kidney coefficient, beta2-MG and renal morphology basically recovered to the normal levels after the drug withdrawal for 4 weeks.
CONCLUSIONThe administration of BDSJS for consecutively 4 weeks can cause mercury accumulation in blood and mainly in kidney. Once the accumulated mercury concentration of kidney reaches a certain level, renal tubular epithelial cells would be injured. 1.1 mg x cm(-2) of BDSJS is proved to be safe and 2.2 mg x cm(-2) can cause mild but reversible injury in the function of kidney which can be recovered after drug withdrawal for 4 weeks.
Acetylglucosaminidase ; urine ; Animals ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; toxicity ; Epithelial Cells ; drug effects ; metabolism ; pathology ; Female ; Kidney Tubules ; drug effects ; metabolism ; pathology ; Male ; Mercury ; blood ; metabolism ; toxicity ; urine ; Rats ; Rats, Sprague-Dawley ; Skin ; drug effects ; injuries ; Time Factors ; beta 2-Microglobulin ; urine

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