1.A proteoglycan-induced spondyloarthritis mouse model and the therapeutic effect of CCN1 monoclonal antibody
Jiajie LI ; Huidan LI ; Jie ZHANG ; Tianhang ZHAI ; Rongfen HUO ; Baihua SHEN ; Weiwei XIN ; Ting LI ; Shuang YE ; Ningli LI
Chinese Journal of Rheumatology 2019;23(8):513-517,后插2
Objective To set up a mouse model of spondyloarthritis,analyzethe clinical phenotype,radiographic and pathological features,and investigate the therapeutic effect of cysteine-rich 61 (CCN1) monoclonal antibody in spondyloarthritis mouse model.Methods Proteoglycan from bovine nasal septum was used for immunization of 14-16 week old female BALB/c mice.CCN1 monoclonal antibody 093G9 or control immunoglobulin (Ig)G were injected to the spondyloarthritis mice.The arthritis scores were analyzed by t test.Peripheral and axial joints disease development was assessed by Micro-CT and histology.Results Proteoglycan immunized mice began to develop peripheral arthritis in the 8th week.The peripheral arthritis score reached the peak (10.5±1.5) in the 11th week,with the inflammation and spur formation of the ankle and knee joint.We found infiltration of inflammation cells in intervertebral discs of the lumbar vertebrae and the caudal vertebrae.Chondrocyte proliferation couldbe seen in the meniscus of knee and lumbar intervertebral discs.In the 18th week,the intervertebral discsof thoracic vertebrae and the cervical vertebrae were also damaged.Abundant chondrocytesgathered in the intervertebra] discs.The inflammation and new bone for-marion of peripheral and axial joints were more severe in control IgG group than 093G9 group.The peripheral arthritis score in the 093G9 group decreased significantly after 2 treatments,[(2.8±1.3) vs (4.2±2.1),t=2.516,P<0.05].The difference in arthritis scores between the two groups was the most significant after 8.treatments,[(2.0±2.0)vs (5.3±2.0),t=4.082,P<0.01].Conclusion The mouse model of spondyloarthritissimulates human spondyloarthritis,including inflammation and new bone formation in p()gheral and axial joints.CCN1 monoclonal antibody can improve the inflammation and new bone formation inspondyloarthritis mouse model.
2.Efficacy and safety of mifepristone combined with misoprostol for termination of pregnancy ;between 8 and 16 weeks of gestation
Jinfeng QIAN ; Xiaoping JING ; Shuying WU ; Shurong ZHENG ; Yi LI ; Mulan REN ; Wen DI ; Huan SHEN ; Baihua DONG ; Qing CHANG ; Huirong SHI ; Chen YAO ; Wei SONG ; Zirong HUANG
Chinese Journal of Obstetrics and Gynecology 2015;(7):505-509
Objective To assess the efficacy and safety of mifepristone combined with oral or vaginal misoprostol for termination of pregnancy between 8 and 16 weeks of gestation. Methods This was a randomized, multi-center, open clinical trial. A total of 625 women at 8-16 weeks of gestation were randomized to receive 200 mg oral mifepristone followed by either oral misoprostol 400 μg every 3 hours or vaginal misoprostol 400μg every 6 hours for a maximum of 4 doses 36-48 hours later. There were 417 women in oral group with 198 at 8-9 weeks and 219 at 10-16 weeks, while 208 women in vaginal group with 99 at 8-9 weeks and 109 at 10-16 weeks. The outcome measures were the success abortion rate, induction to abortion interval, the amount of bleeding, reoccurrence of menstruation and adverse events. Results Abortion rate was significantly higher in vaginal group [98.1% (202/206)] than that in oral group [94.0%(390/415), P=0.023]; concerning termination of pregnancy at 8-9 weeks and 10-16 weeks respectively, there were no significant differences between oral and vaginal groups (P=0.156, P=0.073). The induction to abortion interval was no significant difference in oral and vaginal group in different gestational weeks ( P=0.238, P=0.273). The average induction to abortion interval was (4.1 ± 6.6) hours and (6.0 ± 4.5) hours respectively in terminating 8-9 weeks and 10-16 weeks of gestation. Concerning the amount of bleeding within 2 hours of placenta expulsion, there was significant difference between oral group [(63±46) ml] and vaginal group [(55 ± 45) ml] in terminating 8-9 weeks of gestation (P=0.047), while there was no significant difference between groups in terminating 10-16 weeks of gestation [oral group (76 ± 52) ml versus vaginal group (76 ± 61) ml, P=0.507]. The reoccurrence of menstruation was about 37 days in both oral and vaginal groups. Two cases of incomplete abortion were serious adverse events (SAE) relating to treatment. The common adverse events (AE) of nausea and vomiting were significantly higher in oral group [57.2% (239/417), 36.3% (151/417)] than those in vaginal group [45.4% (94/208), 26.1% (54/208); P=0.005, 0.011]. Conclusion Oral or vaginal misoprostol combined with mifepristone, is effective and safe for termination of pregnancy between 8 and 16 weeks of gestation.
3.The experimental study on the effect of rhTNFR:Fc and methtotrexate-rhTNFR:Fc on joint destruction of collagen-induced arthritis rat
Junlin HU ; Guilin OUYANG ; Huali GAO ; Ningli LI ; Zhiming HUANG ; Zheng HUANG ; Jun XIE ; Baihua SHEN ; Li WANG ; Lianbo XIAO
Chinese Journal of Rheumatology 2011;15(12):843-845
Objective This study is aimed to explore the effect of rhTNFR:Fc and methotrexate (MTX)-rhTN FR:Fc on joint destruction of collagen-induced arthritis ( CIA ) rat by establishing CIA rat model which imitates pathogenic factors of rheumatoid arthritis (RA).Methods CIA rat model were developed by subcutaneous injection of bovine type Ⅱ collagen.The rats with inflammation scores of two or above were randomly divided into four groups:the sterilized water treatment group (0.4 ml/w,intra-peritoneal injection),the MTX treatment group (1 mg/w,intra-peritoneal injection),the rhTNFR:Fc treatment group(0.8 mg Biw,intra-peritoneal injection),the MTX + rhTNFR:Fc treatment group (MTX 1 mg/w and rhTNFR:Fc 0.8 mg Biw,intraperitoneal injection).After treatment for 8 weeks,the rats were sacrificed and took the ankle radiography.Micro-CT scan of proximal tibia was performed and hard-tissue slices were made,and then the ankle's bone damage of each group was observed in order to evaluate trabecular variation and bone quantity changes of proximal tibia.Statisstical analysis was conducted with ANK-q test.Results After treatment for 8 weeks,the percentage of trabecular area and the trabecular number of the rhTNFR:Fc treatment group and the MTX-rhTNFR:Fc treatment were [(29.1±0.3)%,(26.7±0.6)%,(4.4±0.5)/mm,(4.0±0.6)/mm] (P<0.01),which were evidently higher than the sterilized water treatment group and MTX treatment group (P<0.01).The trabecular separation of Etanercept treatment group and MTX-rhTNFR:Fc group was obviously less than the sterilized water treatment group and MTX treatment group [(12.9±0.5)%,(13.2±0.4)% vs (2.0±0.3)/mm,(2.2t0.2)/mm] (P<0.01).Conclusion rhTNFR:Fc and MTX-rhTNFR:Fc can remarkably inhibit joint destruction of CIA rat.And their effect on inhibiting of inflammation and increasing peri-articular bone quantity.In addition,they are effective on inhibiting the reduction of local trabecular structure and increase of trabecular separation.
4.Cyr61 promotes proliferation of fibroblast-like synoviocytes in rheumatoid arthritis and its regulation by inflammatory factor
Jinpiao LIN ; Juanjuan WU ; Li WANG ; Jing ZOU ; Baihua SHEN ; Ningli LI
Chinese Journal of Immunology 2010;26(3):264-269
Objective:To investigate the effect of Cyr61 on the proliferation of Fibroblast-like Synoviocytes (FLS) in rheumatoid arthritis (RA).Methods:Cyr61 expression in synovial tissues (ST) and FLS was examined using Real-time PCR,Western blot and immunohistochemistry simultaneously.FLS were isolated from synovial tissue of RA patients and cultured in vitro.The proliferation of FLS stimulated with synovial fluid (SF) was determined by 3 H-TdR incorporation.Cyr61 protein level in RA SF was detected by ELISA.Results:Cyr61 was over expressed in ST,FLS of RA patients while hardly examined in normal individuals and osterarthritis (OA) patients.Meanwhile,Cyr61 protein level was elevated in SF,which promoted the proliferation of RA FLS.This proliferation was abrogated by knockdown the Cyr61 gene of FLS or neutralizing monoclonal antibody against human Cyr61.Moreover,inflammatory factor IFN-γ and TNF-α up-regulated the expression of Cyr61.Conclusion:These results indicate that the elevated level of IFN-γ and TNF-α in RA SF can promote the proliferation of the FLS derived from RA patients by increasing expression of Cyr61,suggesting that Cyr61 may play an important role in the development of RA.
5.Mouse bone marrow derived mesenchymal stem cells suppress lymphocyte proliferation through co-Inhibitor B7-H1 upregulated by IFN-γ
Huiming SHENG ; Hongyu HUANG ; Yunyu WEI ; Ying WANG ; Li WANG ; Baihua SHEN ; Ningli LI
Chinese Journal of Microbiology and Immunology 2009;29(4):345-350
Objective To study the mechanism of mesenchymal stem cells immunosupression lym- phocyte proliferation via B7-H1/PD-1 pathway upregnlated by IFN-γ. Methods Bone marrow derived mes-enchymal stem cells (MSC) were isolated and purified by repeat adherent passage and detected them multi-potential differentiation in conditioned culture medium. Then MSC were cocuhured with lymphocyte prolifera-tion and assayed the level using γ H-thymidine incorporation. Meanwhile, ELISA measured IFN-γ, TGF-β, TNF-α and IL-10 in the cocuhured supernaatant and analyzed variation of B7-H1 molecular profile in MSC by flow cytometry. At last siRNA technology was deploied to interfere B7-H1 expression and analyzed MSC im-munosuppression on lymphocyte proliferation. Results In vitro the isolated MSC become homogeneous spi-die-shaped adherent cells after five passages, and in conditioned culture medium they could differentiate into adipocytes, osteocytes and chondrocytes. In the eocuhure of MSC with mixed lymphocyte, lymphocyte prolif- eration stimulated by Con A or by anti-CD3/CD28 antibody. The cpm value of the proliferation detected by 3H thymidine incorporation showed MSC suppressed the proliferation significantly (P = 0. 0167, 0. 0081,<0.0001 ) and the suppressive potential in a dose-dependent fashion. In the coeuhured supernatant cyto-kine IFN-T and TNF-α were detected in high concentration, but TGF-β, IL-10 were undetected. Simultane- ously MSC in the coeuhure upregulated B7-H1 expression from basic expression 7% to higher than 70% ( P < 0.05 ). After interfere B7-H1 expression in MSC by specific siRNA, we detected lymphocyte proliferation and got higher cpm by 3H thymidine incorporation ( P < 0. 05 ). Conclusion MSC upregulated B7-H1 mo-lecular expression upon the stimuli of IFN-γ, and through the B7-H1/PD-1 pathway mediated immunosu-pression on lymphocyte proliferation.
6.Mechanism of Treg down-regulation by immunization with attenuated activated autologous T cells
Qiuyu ZHANG ; Juanjuan WU ; Jinbiao LIN ; Zhuangzhuang ZHANG ; Yuan SHI ; Baihua SHEN ; Yan ZHANG ; Ningli LI ; Li WANG
Journal of Shanghai Jiaotong University(Medical Science) 2009;29(10):1148-1151,1156
Objective To explore the mechanism of down-regulation of regulatory T cells (Treg) by immunization with attenuated activated autologous T cells. Methods Aulologous T cells were activated with ConA in vitro. Mice were immunized subcutaneously and inlraperitoneally every 5 days for 3 times (5 ×10~6 per time for each mouse), and the number and function of Treg were examined. PBS was subcutaneously injected for control group. Serum level of anti-mouse CD25 antibody was measured by ELISA. The number and function of Treg was detected by serum adoptive transfer and proliferation and inhibition assays. Results Compared with control group, there were less CD4~+ CD25~+ Foxp3~+ Treg in the mice after immunization (P < 0. 01), the immunosuppression ability decreased (P<0. 01), and the level of anti-CD25 antibody increased (P <0.01). Adoptive transfer of serum from immunized mice to naive mice led to a significant decrease in Treg population and function in recipient mice (P<0. 01). Conclusion Immunization with attenuated activated autologous T cells induces more anti-CD25 antibody, which may further down-regulate CD4~+CD25~+Foxp3~+ Treg expansion and function in vivo.
7.Extra-adrenal pheochromocytoma: report of 34 cases
Ben LIU ; Chaojun WANG ; Songliang CAI ; Liping XIE ; Zhigen ZHANG ; Hai JIANG ; Baihua SHEN ; Suo WANG ; Zhijian SHEN
Chinese Journal of Urology 2008;29(5):296-299
Objective To review the diagnosis and treatment of extra-adrenal pheochromocytoma with a 34cases report. Methods Thirty-four cases of extra-adrenal pheochromocytoma were retrospectively analyzed. Hypertension was observed in 27 cases. Abdominal pain was seen in 10 patients and intermittent hematuria in 2 patients. Serum and urinary catecholamine and urinary VMA were measured in 34 cases. The level of serum or urinary catecholamine elevated in 20 cases and urine VMA elevated in 24 cases. Thirty-four cases had ultrasound examination,25 cases underwent CT scan and 6 cases underwent MER scan.Results Pheochromocytomas of 12 cases were located in the renal hilum, 2 in the lower pole of the left kidney, 1 in the posterior aspect of the inferior vena cava, 3 in the interaortocaval region, 2 in the anterior aspect of the abdominal aorta, 1 in the anterior of the right common iliac artery, 1 in the hilum of the liver, 1 in the posterior o{ the pancreas, 2 in the bladder wall, 1 in the posterior of the descending colon, and 8 cases of multifoci. Twenty-two cases of extraadrenal pheochromocytoma were benign and 12 cases were malignant. Thirty cases were followed up from 6 months to 13 years. Among 27 cases with hypertension, the blood pressure of 22 patients returned to normal and 5 cases were still hypertensive. Nine cases of malignant pheochromocytoma all had tumor recurrence or metastases at one year postoperatively. Six patients died during followed-up from 6 months to 3 years, including 3 cases died of cerebral hemorrhage and 3 cases of tumor metastases. Three cases got stable with 131Ⅰ-MIBG radiotheraphy.Conclusions The accurate detecting extra-adrenal pheochromocytoma is difficult. CT scan could be reliable in localizing the lesions. Surgical resection of the tumor could be the best therapy. Patients of malignant extra-adrenal pheochromocytoma may be treated with 131Ⅰ-MIBG after surgical therapy.
8.Comparison of transperitoneal and extraperitoneal laparoscopic radical prostatectomy
Shuo WANG ; Hang HUANG ; Dan XIA ; Geming CHEN ; Danbo FANG ; Baihua SHEN ; Baiye JIN ; Songliang CAI ; Liping XIE
Chinese Journal of Urology 2008;29(5):329-331
Objective To compare the clinical features and results between transperitoneal laparoscopic radical prostatectomy and extraperitoneal laparoscopic radical prostatectomy.Methods Thirty-three prostate cancer patients treated with laparoscopic radical prostatectomy. Among them,21 cases had been done transperitoneally and 12 cases had been done extroperitoneally. The two different approaches were evaluated and compared in respects of operating time, estimated blood loss, complications during surgery, postoperative complications, intestinal function recovery time, catheterization time and length of hospital stay.Results All the surgeries had completed successfully without conversion to open surgery. For transperitoneal approach and extraperitoneal approach, the operating time was (299±46)min and (309±64)min, blood loss was (618±448)ml and (677±469)ml. There were 3 cases with severe blood loss, 2 cases with bladder injuries and 1 case with ureteral injury in transperitoneal approach group. There were 1 case with severe blood loss, 1 case with obturator never injury, 1 case with cysto-ureteral injury and 1 case with peritoneum injury in extraperitoneal approach group. For transperitoneal approach and extraperitoneal approach,the catheterization time was(14.6±3.8)d and (12.3±2.9)d, intestinal function recovery time was (2.7±0.7)d and (2.1±0.5)d, length of hospital stay was (17.0±3.6)d and (11.2±3.5)d, respectively.Conclusions Laparoscopic radical prostatectomy is feasible and safe in clinical practice. Extraperitoneal approach has better vision, less impact on abdominal organs, faster recovery and shorter hospital stay comparing to transperitoneal approach.
9.Effect and mechanism of alpha1-adrenoceptor blocker combined with antibiotics for chronic prostatitis.
Baihua SHEN ; Xiaodong JIN ; Songliang CAI ; Jun CHEN ; Geming CHEN ; Weiping ZHAO ; Xin SUN
National Journal of Andrology 2004;10(7):518-520
OBJECTIVETo investigate the effect and mechanism of alpha1-adrenoceptor blocker combined with antibiotics in the treatment of chronic prostatitis.
METHODSEighty patients with chronic prostatitis were divided into two groups, one treated with alpha1-adrenoceptor blocker (Terazosin 2 mg qn) and Levo-ofloxacin (0.2 bid), and the other given Levo-ofloxacin (0.2 bid) alone for 6 weeks. Chronic prostatitis symptom index (CPSI), urodynamic data and prostatic secretion examination were compared before and after treatment.
RESULTSThe CPSI score of the treated group decreased from 31.8 +/- 7.4 to 15.5 +/-6.6, while that of the control group decreased from 30.9 +/- 7.1 to 21.4 +/- 6.2. There was significant difference between the two groups (P < 0.05). The maximum flow rates before and after the combined treatment were 16.5 +/- 6.3 ml/s and 20.4 +/- 4.6 ml/s, while those before and after Levo-ofloxacin administration were 16.1 +/-5.8 ml/s and 17.3 +/- 6.8 ml/s. The difference was significant (P < 0.05). The maximum urethral pressure of the combined treatment group decreased from 92.5 +/- 15.3 cm H2O to 72.5 +/- 13.4 cm H2O, while that of the control group decreased from 93.2 +/- 14.8 cm H2O to 91.7 +/- 13.6 cm H2O.
CONCLUSIONAlpha1-adrenoceptor blocker can lower the intraurethral pressure, which prevents urine from refluxing to the prostate. Alpha1-adrenoceptor blocker combined with antibiotics is effective for chronic prostatitis.
Adrenergic alpha-1 Receptor Antagonists ; Adrenergic alpha-Antagonists ; administration & dosage ; Adult ; Anti-Bacterial Agents ; administration & dosage ; Chronic Disease ; Drug Therapy, Combination ; Humans ; Male ; Middle Aged ; Prostatitis ; drug therapy ; physiopathology ; Urodynamics
10.Clinical analysis of 15 cases of Paget's disease of the scrotum.
Baihua SHEN ; Hongzhou MENG ; Liping XIE ; Songliang CAI ; Shuo WANG ; Zhigen ZHANG ; Yimin WANG
National Journal of Andrology 2004;10(6):437-442
OBJECTIVETo study the clinicopathologic features and treatment of Paget's disease of the scrotum.
METHODSFifteen cases of Paget's disease of the scrotum, pathologically diagnosed and successfully treated by surgery from 1987 to 2003, were studied retrospectively.
RESULTSTypical pathological features were observed in all the patients. Thirteen cases were followed up for 0. 5 approximately 13 years, of whom 1 case relapsed within 3 years, 2 died of metastasis after 2 years, and 3 died of cardiovascular diseases, with no recurrence in the others.
CONCLUSIONEarly biopsy and extensive excision of the scrotal lesion is the first choice of treatment for Paget's disease, with good operative effect and satisfactory prognosis. A 2nd operation could be considered for patients of local relapse.
Aged ; Aged, 80 and over ; Genital Neoplasms, Male ; pathology ; surgery ; Humans ; Male ; Middle Aged ; Paget Disease, Extramammary ; pathology ; surgery ; Retrospective Studies ; Scrotum ; pathology

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