1.Expression of extracellular matrix metalloproteinase inducer CD147 and MMP-9 in hepatocellular carcinoma and its clinical significance
Zhenyu LI ; Weilin WANG ; Zheping FANG
Tumor 2010;(3):215-219
Objective:To study the expression of extracellular matrix metalloproteinase (MMP-9) inducer CD147 and MMP-9 protein in hepatocellular carcinoma (HCC) and explore their correlation with invasion, metastasis, and prognosis of HCC.Methods:SP immunohistochemistry was used to evaluate the expression of CD147 and MMP-9 in 83 HCC tissues and 15 normal liver tissues. Results:The positive rate was 73.5% for MMP-9 and 68.7% for CD147, significantly higher than normal tissues (MMP-9: 6.7%;CD147: 0%, P<0.05). Expressions of CD147 and MMP-9 were positively correlated with the tumor size, pTNM stages, differentiation degree, the portal vein cancer embolism, and postoperative recurrence (P<0.05), but not with the patient's age, gender, the serum level of alpha-fetal protein (AFP), and the Child-Pugh grades. Patients with positive expression of CD147 and MMP-9 had shorter survival time than those with negative expression of CD147 and MMP-9. Expression of CD147 was positively related with expression of MMP-9 in HCC tissues.Conclusion:CD147 and MMP-9 had positive correlation with tumor size, pTNM stages, differentiation degree, portal vein cancer embolism, and postoperative recurrence. Detection of the expression of CD147 and MMP-9 may be helpful to make a comprehensive prediction of the prognosis of HCC.
2.Advances of relationship between protein O-GlcNAcylation and glucose metabolism in tumors
Weilin ZHANG ; Xinyi WANG ; Fang YAN
Journal of China Pharmaceutical University 2019;50(2):127-134
O-GlcNAcylation is the addition of a single N-acetylglucosamine(GlcNAc)moiety to the hydroxyl groups of serine or threonine residues of nuclear and cytoplasmic proteins. The transcription factors, kinases of the metabolic pathways and some cytoplasmic enzymes can be O-GlcNAcylated to affect cell transcription, signal transduction, cell metabolism and other biological functions. Abnormal glucose metabolism of tumors has been a hotspot in the research field of tumor pathogenesis and therapeutic targets recently. O-GlcNAclation regulates the glucose metabolism of tumor by affecting the activity of kinases in the metabolic pathway, which is closely associated with the abnormal glucose metabolism of tumor. The abnormal O-GlcNAcylation is one of the potential reasons of cancer. In this review, in order to provide a theoretical reference for developing anti-tumor targets and drugs targeting O-GlcNAc modification, we briefly summarized how O-GlcNAcylation regulated glucose metabolism on glucose metabolism, glucose uptake, glycolysis, pentose phosphate pathway and tricarboxylic acid cycle in cancer cell.
3.Mid-term and long-term safety and efficacy of TVT-O for the treatment of stress urinary incontinence
Weilin FANG ; Zhengwang ZHANG ; Weiqing QIAN ; Jiqiong ZHENG ; Maofei YE
Chinese Journal of Urology 2015;(10):782-785
Objective To evaluate the complications and long-term efficacy of inside-out transobturator transvaginal tape ( TVT-O) for the treatment of stress urinary incontinence ( SUI) .Methods From January 2008 to December 2013,236 consecutive female patients (mean age 56 ±9 years,range 44-88 years)with the symptom of incontinence when abdominal pressure increasing (such as walking), underwent TVT-O operation.All these patients needed pads and were diagnosed with SUI by cough test and Marshall -bonny test before surgery , with the mean international consultation committee on incontinence questionnaire short form ( ICI-Q-SF) score of 15.6 ±3.9.Two grouping methods were used:the mid-term group including patients whose follow-up time was between 6 months and 3 years, the long-term group including patients whose follow-up time >3 years,the group of patients who underwent TVT-O only and the group of patients who underwent TVT-O plus pelvic floor repair at the same time . Their clinical and follow-up data , intraoperative and postoperative complications , subjective and objective effects were recorded and analyzed.Results Of these 236 patients,there were 1 case of bladder perforation (0.4%) and 1 case of intraoperative sling exposure to vagina ( 0.4%) .Postoperative complications included 36 ( 19.1%) groin/puncture point pain ,18 (9.5%) de novo frequency of micturition ,8 (4.2%) urinary retention /difficulty of urination.All the complications were relieved after symptomatic treatment or surgery except 2 cases of urinary retention/difficulty of urination.Their symptom kept existing after urethral dilatation and sling dissection and long-term intermittent self-catheterization was needed .One hundred and eighty-nine patients completed more than six months of follow-up, with mean follow-up time of ( 35.0 ±12.5 ) months.One hundred and sixteen (61.4%) cases was arranged to mid-term group and 73(38.6%) was arranged to long-term group.88.9%patients ( 168/189 ) were cured objectively and 9.5% patients ( 18/189 ) improved. There was also a significant subjective improvement ( ICI-Q-SF scores:15.6 ±3.9 preoperative versus 6.7 ± 2.3 postoperative,P<0.01).There was no significant difference of both objective and subjective efficacy between mid-term group and long-term group ( cured +improved rate 97.4% versus 95.9%;ICI-Q-SF scores 14.3 ±2.8 versus 16.7 ±3.4 preoperative ,5.8 ±1.2 versus 7.9 ±2.0 postoperative , P>0.05 ) . Patients who underwent TVT-O and those who underwent TVT-O +pelvic floor repair had no significant difference in efficacy (cured +improved rate 97.8%versus 100.0%,P>0.05).Conclusion TVT-O is a safe,effective and durable treatment for SUI , whether or not with concomitant procedure of pelvic floor repairment.
4.PROTECTIVE EFFECT OF PROTOPORPHYRIN ON THE LIVER INJURY IN RABBITS AND MICE
Shusen LING ; Qun FANG ; Qin YANG ; Weilin SNN
Chinese Pharmacological Bulletin 1986;0(04):-
Studies were made on the effect of protoporphyrin in treating the acute liver injury induced by carbon tetrachloride ( CCl4 ) in rabbits and on the liver blood flow, biosynthesis of DNA and protein in liver of mice. The results showed that the protoporphy-rin was able to protect the liver remarkable as evidenced by his-tological studies. And it could inhibit the elevation of serum glut-amic-pyruvic transaminase ( SGPT ) , serum glutamic - oxaloacetic transaminase ( SGOT ) and serum ?-glutamyl- transpeptidase ( S?- GT)also. Protoporphyrin could regulate the metabolism of serum amino -acids in rabbits intoxicated by CCl4 as well. Furthermore,protoporphyrin can improve biosynthesis of DNA and liver protein and it may increase the blood flow in the liver of the mice.
5.Preliminary application of MR diffusion weighted imaging in the diagnosing and evaluating therapeutic effect of autoimmune pancreatitis
Jiacheng ZHANG ; Chen ZHANG ; Zhenghan YANG ; Weilin TANG ; Jinzhou FANG ; Zhongfei XU ; Ye TAN ; Jie ZHU ; Min CHEN ; Cheng ZHOU
Chinese Journal of Radiology 2014;(6):484-488
Objective To investigate the role of DWI in differentiating autoimmune pancreatitis ( AIP) from pancreatic cancer ( PC) , and in the therapeutic effect evaluation of AIP.Methods DWI data of 26 cases with AIP , 29 cases with PC and 30 cases with normal pancreas ( NP ) were analyzed retrospectively.The distribution type and signal feature of lesions in cases with AIP or PC were evaluated by Chi-squared test.ADC values were measured and compared among 3 groups by Kruskal-Wallis test.ADC values of AIP and PC were analyzed by using ROC curve to determine the optimal threshold and diagnostic efficiency.ADC values were compared in AIP ( n=15 ) before and after steroid therapy by paired t test.Results Diffuse lesions were detected in 21 cases with AIP and 3 cases with PC, while focal lesions in 5 cases with AIP and 26 cases with PC (χ2 =27.64, P<0.01).On DWI, most of AIP (n=19) and PC (n=24) showed hyper-intense signal, while a few of AIP (n=7) and PC (n =5) showed iso-intense signal (χ2 =0.75, P>0.05).The median ADC values of AIP, PC and NP were 1.15 ×10 -3,1.35 × 10 -3 ,1.59 ×10-3 mm2/s, respectively; and the difference was statistically significant ( H=45.60, P <0.01).ROC analysis yielded an optimal ADC cutoff value of 1.255 ×10 -3 mm2/s (80.8% sensitivity, 79.3%specificity and 0.871 area under curve for the diagnosis of AIP ).ADC values of AIP ( n=15) were markedly increased from the baseline (1.10 ±0.19) ×10 -3 to (1.57 ±0.12) ×10 -3 mm2/s after steroid therapy (t=-10.14, P<0.01).Conclusions DWI may be useful for diagnosing and evaluating the effect of steroid therapy in AIP.ADC values of AIP were significantly lower than those of pancreatic cancer and normal pancreas.After steroid therapy , ADC values were markedly increased in AIP.
6.Biological activity and pathogenicity of M23 superfamily metalloendopeptidases of Leptospira interro-gans
Yingying ZHANG ; Yumei GE ; Jiaqi FANG ; Xu′ai LIN ; Weilin HU ; Jie YAN
Chinese Journal of Microbiology and Immunology 2017;37(10):753-760
Objective To understand and determine the biological activity and pathogenicity of metalloendopeptidases encoded by LA2582 and LA2901 genes of Leptospira interrogans(L.interrogans) sero-group Icterohaemorrhagiaeserovar Lai strain Lai. Methods Structures and functions of LA2582 and LA2901 genes were analyzed by using bioinformatic software. Prokaryotic expression systems for expressing the extra-cellular regions of LA2582 and LA2901 genes were generated. The target recombinant expression products, rLA2582 and rLA2901,were extracted by Ni-NTA affinity chromatography. The Azo-casein-hydrolyzingactiv-ity of rLA2582 and rLA2901 was detected by spectrophotometry. Activities of rLA2582 and rLA2901 in the hydrolysis of Dabsyl-Leu-Gly-Gly-Gly-Ala-Edans, a fluorescence-labeling pentapeptide substrate, were de-tected by fluorospectrophotometry,and then the Km and Kcat values were determined. SDS-PAGE and spec-trophotometry were performed to detect the activities of rLA2582 and rLA2901 in hydrolyzing extracellular matrix molecules such as collagen type-Ⅰ (COL1), fibronectin (FN) and Congo red-labeling elastin (ELN). Real-time fluorescent quantitative RT-PCR(qRT-PCR) and Western blot were respectively used to measure the expression of LA2582 and LA2901 genes at mRNA and protein levels after infecting human um-bilical vein endothelial cells(HUVEC) with L. interrogans strain Lai. Results The gene products of LA2582 and LA2901 genes were identified as the signal peptide and matrix metalloproteinase motif HXH-containing Zn2+-dependent Gly-Gly metalloendopeptidases belonging to the M23 superfamily. rLA2582 and rLA2901 did not hydrolyze Azo-casein (Km=126.54 μmol/L, Kcat=4.67/s), but could hydrolyze the pentapeptide substrate (Km=190. 25 μmol/L, Kcat 4. 86/s). rLA2582 and rLA2901 could hydrolyze COL1, FN and ELN. Expression of LA2582 and LA2901 genes at both mRNA and protein levels was signifi-cantly increased after infection of HUVEC with L.interrogans strain Lai(P<0.05). Conclusion The prod-ucts of LA2582 and LA2901 genes of L.interrogans strain Lai are Zn2+-dependent M23 metalloendopeptidas-es, which can hydrolyze multiple ECM molecules and are closely associated with the leptospiral invasiveness.
7.Imaging characteristics of autoimmune pancreatitis:MRI versus CT
Ye TAN ; Jinzhou FANG ; Zhenghan YANG ; Lei JIANG ; Weilin TANG ; Duo ZHANG ; Guang LI ; Jun ZHANG ; Xiaohua YE ; Min ZHANG ; Cheng ZHOU
Chinese Journal of Radiology 2009;43(8):835-839
ncreatic enlargement, MRI is comparable to CT.
8.CdaR-DAC signaling systems regulating the synthesis of a second messenger c-di-AMP in Leptospira interrogans
Bao FANG ; Yang LI ; Jie YAN ; Weilin HU
Chinese Journal of Microbiology and Immunology 2018;38(12):881-885
Objective To analyze the activity of diadenylate cyclase ( DAC) encoded by LA3304 gene of Leptospira interrogans ( L. interrogans) and to investigate the influence of CdaR encoded by LA3303 gene on DAC activity. Methods The LA3304 gene in L. interrogans serogroup Icterohaemorrhagiae serovar Lai strain Lai was amplified by PCR and inserted into a prokaryotic expression system for expressing DAC. The expressed recombinant protein, rDAC, was purified by Ni-NTA affinity chromatography. High Perform-ance Liquid Chromatography ( HPLC) was used to measure the synthesis of c-di-AMP from ATP by rDAC in vitro. Bacterial two-hybrid analysis was used to detect the interaction between CdaR and DAC. Prokaryotic co-expression system was constructed and used in combination with HPLC to analyze the role of CdaR in acti-vating DAC. Results The constructed prokaryotic expression system for LA3304 gene of L. interrogans strain Lai could highly express the rDAC upon the induction of IPTG. The purified rDAC showed high purity with a single protein band in gel as indicated by SDS-PAGE. rDAC could synthesize c-di-AMP from ATP in vitro. CdaR interacted with DAC and enhanced the activity of DAC (P<0. 05). Conclusion DAC encoded by LA3304 gene was a diadenylate cyclase that could convert ATP into c-di-AMP. CdaR promoted the acti-vation of DAC and formed a CdaR-DAC system with DAC. The system was involved in the synthesis of c-di-AMP in L. interrogans.
9.Application of modified laparoscopy in repair of high complex vesical vagina fistula
Chen JIANG ; Qibo FU ; Weilin FANG ; Jianwei LYN ; Dongming LIU ; Wei XUE ; Yiran HUANG
Chinese Journal of Urology 2018;39(8):565-568
Objective To evaluate the efficacy of modified abdominal laparoscopy in the repair of complex vesical vaginal fistula after total hysterectomy.Methods The clinical data of 58 cases of urinary bladder and vagina fistula in our hospital from April 2014 to December 2017 were retrospectively analyzed,of which 32 cases were repaired by ordinary abdominal laparoscopy from April 2014 to February 2016 and 26 cases were repaired by modified abdominal laparoscopy from March 2016 to June 2017.On the basis of the original laparoscopy,the modified transabdominal laparoscopy enlarged the free range between the vaginal stump and the bladder,separated the anterior vaginal wall from the bladder completely and dissociated the retrovaginal peritoneum,wrapping around the vaginal stump to make the peritoneum.The median age of ordinary group was 52 (range:33-67)years old,the median course of disease was 12 (range:3-40) months,and the size of fistula was (25.5 ± 10.3) mm.The median age of modified group was 50 (range:37-65) years,the median course of disease was 11.5 (range:3-36) months,and the size of the fistula was (26.3 ± 9.1) mm.The operation time,bleeding volume,the time of hospitalization,the rate of complications and the success rate of the operation were compared.Results The operation time of the two groups was successfully completed.The operation time of the modified group [(164.2 ± 21.2) min] was significantly shorter than that of the common group [(201.4 ± 25.8) min],and the difference was statistically significant (P < 0.01).In the modified group,the cure rate (100.0%,26/26) was higher than that in the normal group (84.4%,27/32,P < 0.05).There was no significant difference in the amount of intraoperative bleeding[50 (10-100) ml vs.55 (5-110) ml],hospitalization time [(9.1 ± 1.7) d vs.(10.0 ± 1.8) d],postoperative infection [19.2% (5/26) vs.15.6% (5/32)],urinary incontinence [7.7% (2/26) vs.9.4% (3/32)],urinary frequency [15.4% (4/26) vs.21.9% (7/32)],intestinal obstruction [3.8% (1/26) vs.9.4% (3/32)] between the modified group and common group (P > 0.05).Conclusions The modified transabdominal laparoscopic mode shortens the operation time,and improves the cure rate of the operation.Satisfactory results are recommended for the repair of high complex bladder vagina fistula.
10.Clinical observation of adjusting middle urethral sling tension through anatomic position during RMUS
Jiayi LI ; Qixiang SONG ; Weilin FANG ; Yiyuan GU ; Yunyue GUO ; Wei ZHANG ; Lei XU ; Wei XUE
Chinese Journal of Urology 2022;43(9):675-680
Objective:To investigate the safety and effectiveness of tension adjustment technique using anatomical landmarks during retropubic midurethral synthetic sling.Methods:The data of 36 consecutive female patients with urinary incontinence, who had underwent retropubic midurethral synthetic sling procedure from January to August 2019 were analyzed retrospectively. The mean age was (60.83±7.93) years old and the body mass index was (24.43±2.44) kg/m 2. Among the recruited subjects, 36 had positive stress test and Marshall-Marchetti test. 20 (55.6%) were pure stress urinary incontinence, and 16 (44.4%) were mixed urinary incontinence. The severity of incontinence was classified into mild (5 cases, 13.9%), moderate (14 cases, 38.9%), severe (13 cases, 36.1%) and very severe (4 cases, 11.1%) using one-hour pad tests. Urodynamics were performed in 17 cases, with 5 (29.4%) presented detrusor overactivity, 3 (17.7%) possessed intrinsic sphincter deficiency. For each case, the tension of the sling was adjusted based on the anatomical landmarks, i. e. using an angled clamp attached closely to the pubic symphysis ventrally and the tip parallel to the edge of hymen dorsally. All patients were catheter-free right after the procedure. The subjective and objective effectiveness, and safety (the rate of urinary retension after surgery and postvoid residual volume 3 months later) were evaluated.The subjective cure rate was was defined as complete leakage free or very mild leakage during excessive bladder filling and fierce cough. The subjective effectiveness was defined as over 50% improvement of the leakage symptom. The objective cure rate was defined as a negative stress test. Results:For all 36 patients, the median hospital stays was 8 (5-95)h. No bladder perforation or transfusion cases. All patients were catheter-free right after the procedure, with no incidence of urinary retention. 27 patients completed a 3-month follow-up, with 22 had post-void residual data, 23 had subjective effectiveness data and 23 had objective effectiveness data. The median post-void residual was 7.5 (5-64) ml, subjective cure rate was 91.3% (21/23), and objective cure rate was 95.7% (22/23). 8.7% (2/23) reported difficult urination alleviated without the necessity of clinical interference. No urethra erosion or vagina extrusion was found. At 2-year follow-up, 34 patients completed assessment by phone. The subjective cure rate was 91.2% (31/34), with only 2.9% (1/34) reported difficult urination. Besides, at 3-month follow-up, there was no difference regarding the subjective cure rate [100.0%(12/12) vs. 81.8%(9/11)]or objective cure rate [91.7%(11/12) vs. 100.0%(11/11)] between patients with stress and mixed incontinence. No difference was noted among patients with mild, moderate, severe and very severe leakage[75.0% (3/4) vs. 100.0%(6/6) vs. 90.0%(9/10) vs. 100.0%(3/3)]. Of the 12 cases with urodynamic records, the presence of detrusor overactivity [66.7%(2/3) vs. 88.9%(8/9)] or intrinsic sphincter deficiency [0(0/1) vs. 90.9%(10/11)] did not significantly affected the cure rate of the procedure. At 2-year follow-up, there was no difference regarding the subjective cure rate between patients with stress and mixed incontinence [94.7%(18/19) vs. 86.7%(13/15)]. No difference was also noted among patients with mild, moderate, severe and very severe leakage[80.0%(4/5) vs. 100.0%(13/13) vs. 83.3%(10/12) vs. 100.0%(4/4)]. Of the 16 cases with urodynamic records, the presence of detrusor overactivity [60.0%(3/5) vs. 90.9%(10/11)]or intrinsic sphincter deficiency [66.7%(2/3) vs. 84.6%(11/13)]did not significantly affected the cure rate of the procedure.Conclusions:Tension adjustment using anatomic landmarks during sling procedure is safe and feasible for urinary incontinence, with minimum complications and residual volume, and high subjective/objective cure rate.