1. Activation of wnt/β-catenin signaling enhanced stemness of prostate cancer cells
Tumor 2019;39(7):533-567
Objective: To explore the relationship between the activity of Wnt/β-catenin signaling pathway and prostate cancer stem cells by utilizing a Wnt/β-catenin signaling reporter system. Methods: Immunofluorescence staining was used to explore the activation of Wnt/β-catenin signaling pathway in prostate cancer. Wnt/β-catenin signaling reporter plasmid 7TGP carrying T cell specific transcription factor (TCF) binding site and enhanced green fluorescent protein (GFP) was transfected into prostate cancer PC3 and DU145 cells by liposomes, respectively. Furthermore, the top 5% (GFP+) and bottom 5% (GFP-) groups of PC3 and DU145 cells according to the fluorescent intensity of GFP were collected via flow cytometry. Then Western blotting assay was used to compare the expression level of activated β-catenin protein in the nucleus of GFP+ and GFP- cell groups. The real-time fluorescent quantitative PCR was used to detect the expressions of Wnt/β-catenin signaling downstream target genes in GFP+ and GFPcell groups. Sphere formation assay and real-time fluorescent quantitative PCR were used to compare the stemness of GFP+ and GFP- cells. Results: The activity of canonical Wnt signaling pathway was low in most of prostate cancer cells, in which β-catenin was not activated and translocated to the nucleus. While β-catenin was increasingly translocated to the nucleus in a small percentage of prostate cancer cells resulting in high activation of Wnt signaling pathway. PC3-GFP+ and DU145-GFP+ cells had more expression of nuclear β-catenin comparing with the corresponding GFP- cells (both P < 0.05), and the expression level of Wnt signaling pathway down-stream target gene Axis inhibition protein 2 (AXIN2) was up-regulated (both P < 0.05). In addition, the expression levels of cancer stem cell markers including B-cell-specific moloney leukemia virusinsert site 1 (BMI1) and aldehyde dehydrogenase family 1 member A1 (ALDH1A1) were up-regulated in PC3-GFP+ and DU145-GFP+ cells comparing with the corresponding GFP- cells (all P < 0.05). The sphere formation capacity was remarkedly up-regulated in PC3-GFP+ and DU145-GFP+ cells comparing with the corresponding GFP- cells (both P < 0.05). Conclusion: Prostate cancer cells with higher activity of Wnt/β-catenin signaling show the enhanced stemness.
2.Diagnosis value of urodynamics in patients with benign prostate hypertrophy
Zhi-hua ZHOU ; Ya-wei WANG ; Liang YING ; Ming LUO ; Fang QIU
Journal of Medical Biomechanics 2010;25(1):E074-E076
Objective To evaluate the diagnosis value of urodynamics in patients with benign prostate hypertrophy(BPH).Methods With urodynamic device,the full set of urodynamic exam was administrated in 427 patients with BPH,and the externalsphincter urethral myogram was monitored simultaneously in pressure-flow studies(PFS).The umdynamic finding such as Qmax 、Pdet-Qmax、Popen、DS(descending slope) and post-voiding residual(PVR)were recorded,as well as the situation of bladder detrusor constraction and bladder compliance and urethral sphincter coordination. The bladder outflow obstruction was diagnosed by A-G nomogram,P-Q plot and DS.The IPSS score and prostate volume were also acquired. Results The diagnostic rate of BOO is 81.5%,among them concomitantly detrusor muscle impair in 117 cases(27.4%), decreased bladder compliance in 162 case (37.9%),urethral sphincter dyssynergia in 148 cases(34.7%),and unstable bladder in l64 cases (38.4%). The increase degree of BOO show an increasing tendency with urodynamic findings such as Qmax ,Pdet-Qmax,Popen,DS and IPSS score and prostatic volume respectively,however a decreasing tendency with Qmax and bladder compliance. Conclusions The urodynamic exam plays an important role in diagnosis of BOO.There is a positive relation among degree of BOO with urodynamic finding such as Pdet-Qmax,Popen,DS and IPSS score and prostatic volume,however,negative relation with Qmax and bladder compliance respectively.
3. Research progress about influence of patellofemoral osteoarthritis on effectiveness of unicompartmental knee arthroplasty
Chinese Journal of Reparative and Reconstructive Surgery 2019;33(3):377-381
Objective: To summarize the current research progress about influence of patellofemoral osteoarthritis on clinical outcome of unicompartmental knee arthroplasty (UKA). Methods: The recent related literature was extensively reviewed and summarized, including pros and cons to regard the patellofemoral osteoarthritis as the contraindication. Results: Previous studies regarded patellofemoral osteoarthritis as the contraindication of UKA. Most of current researches show that the damage to the articular cartilage of the patellofemoral joint to the extent of full-thickness cartilage loss has no influence on outcome of UKA. There is no correlation between preoperative anterior knee pain or medial patellofemoral joint degeneration and the clinical outcome. However, lateral subluxation of the patella has an adverse impact on postoperative curative effect. Degeneration of the lateral patellofemoral joint may be a risk factor of the outcome. Conclusion: Patellofemoral osteoarthritis should not be the absolute contraindication of UKA. The effect of degeneration of the lateral patellofemoral joint is not clear at present, and still needs further studies in the future.
4. Peripheral monocyte count: An independent diagnostic and prognostic biomarker for prostate cancer-A large Chinese cohort study
Asian Journal of Andrology 2017;19(5):579-585
Increasing evidence indicates that inflammation may play important roles in tumorigenesis and progression, and an elevated peripheral monocyte count predicts a poor prognosis in various types of malignancies. Here, we evaluate the roles of peripheral monocyte count in the diagnosis and prognosis for prostate cancer in Chinese patients. A total of 1107 consecutive patients who had undergone prostate biopsy and 290 prostate cancer patients receiving androgen deprivation therapy as first-line therapy were retrospectively analyzed. The parameters were measured at the time of diagnosis. Univariate and multivariate logistic regression analyses were performed to identify the independent predictors of a positive biopsy. Patients were categorized in two groups using a cutoff point of 0.425 × 109 l-1 as calculated by the receiver-operating curve analysis for prognosis. Univariate and multivariate Cox regression analyses were performed to determine the associations of monocyte count with progression-free survival, cancer-specific survival, and overall survival. Multivariate logistic regression analyses showed that monocyte count, age, prostate-specific antigen (PSA), free/total PSA, and prostate volume were independent predictors for prostate cancer. Multivariate Cox regression analyses identified an elevated monocyte count as an independent prognostic factor for worse cancer-specific survival (hazard ratio = 2.244, P < 0.05) and overall survival (hazard ratio = 1.995, P < 0.05), but not progression-free survival (P = 0.117). Our results indicated that an elevated monocyte count was an independent diagnostic biomarker for prostate cancer, and pretreatment peripheral monocyte count might play a significant role in the prognosis of prostate cancer patients treated with androgen deprivation therapy.
5. Analysis of Tim-3/Gal-9 expression and T cell infiltration in adenocarcinoma of the esophagogastric junction
Journal of Shanghai Jiaotong University(Medical Science) 2020;40(6):848-855
Objective • To detect T cell immunoglobulin mucin 3 (Tim-3) and galectin 9 (Gal-9) expression as well as CD3+ T cells and CD8+ T cells infiltration in the tumor tissues of adenocarcinoma of the esophagogastric junction (AEG), and analyze their correlations with the patients' clinical characteristics and survival prognosis. Methods • A retrospective case study was used to collect clinical data and follow-up data of 116 AEG patients who were admitted to Renji Hospital, Shanghai Jiao Tong University School of Medicine from Dec. 2005 to Dec. 2013. Tim-3, Gal-9, CD3, and CD8 protein expressions were detected by immunohistochemistry in the tumor tissues, and the clinical characteristics and prognosis were compared among the patients with different levels of protein expression and T cells infiltration. Results • The results of immunohistochemistry showed that Tim-3 mainly expressed in the infiltrating immune cells, and Gal-9 mainly expressed in the tumor cells. The analysis on the clinical characteristics revealed that Tim-3 expression level was related to the Siewert classification (P=0.030) and CD8+ T cells infiltration level was related to the tumor TNM stage (P=0.042). The results of survival analysis showed that the patients with high level of CD8+ T cells infiltration had a better survival prognosis (P=0.047). However, there was no difference in the prognosis among the patients with different Tim-3 and/or Gal-9 expression levels or with different CD3+ T cell infiltration levels. Conclusion • AEG patients with high level of CD8+ T cells infiltration usually have earlier TNM stages and better prognosis. There is no significant difference in the prognosis of AEG patients with different Tim-3/Gal-9 expression levels.
6. Effects of levosimendan on kidney injury in ventricular fibrillation-induced cardiac arrest rats
Journal of Shanghai Jiaotong University(Medical Science) 2019;39(12):1360-1365
Objective • To investigate the effects of levosimendan on kidney injury in the rat model of cardiopulmonary resuscitation. Methods • Twentyfive healthy adult male SD rats were randomly divided into three groups, which were sham group (S group, n=5), levosimendan group (L group, n=10) and control group (C group, n=10). Cardiac arrest and cardiopulmonary resuscitation procedure were created in L group and C group by inducing ventricular fibrillation. L group was treated with levosimendan during and after resuscitation, while C group and S group were given equivalent volume of saline solution. S group was not induced into cardiac arrest and resuscitation. Serum interleukin-6 (IL-6), IL-10, tumor necrosis factor-α (TNF-α), creatinine (SCr), blood urea nitrogen (BUN) and cystatin-C (CysC) levels were compared between L group and C group at 1, 4 and 6 h after resuscitation.Three groups of rats were sacrificed, and the pathological changes of kidney tissues were observed at 6 h after resuscitation. Results • All rats were resuscitated successfully. No differences were found between the three groups about baseline data. After resuscitation, compared with S group, the levels of serum inflammatory cytokines and kidney function indicators increased dramatically (all P<0.05) in the other two groups. In resuscitation after 1, 4 and 6 h, the levels of IL-6 and TNF-α in L group were lower than those in C group, but IL-10 levels were higher in L group (P=0.000, P=0.002, P=0.036) than those in C group, and there were significant differences between the two groups (all P=0.000). In resuscitation after 1, 4 and 6 h, the levels of SCr (P=0.001, P=0.007, P=0.472), BUN (P=0.001, P=0.004, P=0.122) and CysC (P=0.493, P=0.001, P=0.175) were lower in L group than those in C group. Only 1 and 4 hours after resuscitation, the differences in the levels of SCr and BUN were significant, and only 4 hours after resuscitation, the difference in the level of CysC was significant between L group and C group. Both L and C group showed pathological characteristics of severe acute kidney injury, and the pathological injury scores of L group were alleviated compared with those of C group (all P=0.000). Conclusion • Levosimendan can improve kidney injury of cardiac arrest and cardiopulmonary resuscitation model rats.
7. Application value of anti-double stranded DNA antibody in systemic lupus erythematosus by enzyme-linked immunosorbent assay
Journal of Shanghai Jiaotong University(Medical Science) 2019;39(5):530-533
Objective • To investigate the characteristics and clinical application value of anti-double stranded DNA (dsDNA) antibody detected by enzyme-linked immunosorbent assay (ELISA). Methods • 186 patients with systemic lupus erythematosus, 183 autoimmune disease of non-SLE controls, 78 non-autoimmune disease controls and 50 healthy controls were selected. The serum anti-dsDNA antibody was detected simultaneously by the methods of ELISA and radioimmunoassay (RIA) and their diagnostic efficacies for detection were compared. Results • The sensitivities of anti-dsDNA antibody in SLE by RIA and ELISA were 47.31% and 62.90%, respectively. The specificities were 85.85% and 81.67%, respectively. The positive predictive were 66.67% and 67.24%, respectively. The negative predictive were 73.15% and 78.14%, respectively. The anti-dsDNA antibody levels of SLE patients detected by ELISA and RIA both increased with the increase of SLE disease activity index. Conclusion • The specificity of ELISA is similar with RIA in diagnosing SLE, and the sensitivity is higher than RIA, which can screen the patients with SLE. In addition, the two methods are both suitable for monitoring the condition of SLE.
8. Role of On-cells and Off-cells in the rostral ventromedial medulla in pain modulation
Journal of Shanghai Jiaotong University(Medical Science) 2019;39(1):95-98
The rostral ventromedial medulla is one of the key structures in descending pain modulation system. It receives inputs from the thalamus, the periaqueductal gray, and parabrachial nucleus, and sends descending projections through the dorsolateral funiculus and ventrolateral funiculus to the spinal dorsal horns. The rostral ventromedial medulla is thought to be the final relay in descending modulation of pain. The neurons in this region can be classified into On-cells, Off-cells and Neutral cells according to the changes in the firing activity before tail flick. This review mainly focuses on pain modulation functions and potential analgesia mechanisms of On-cells and Off-cells.
9. Value of two-dimensional speckle-tracking echocardiography in accessing myocardial viability and predicting left ventricular remodeling after acute myocardial infarction
Journal of Shanghai Jiaotong University(Medical Science) 2018;38(12):1447-1453
Objective • To evaluate the strain parameters measured by two-dimensional speckle tracking echocardiography (2D-STE) in predicting myocardial segment functional recovery and left ventricular (LV) remodeling. Methods • Eighty-one patients with first acute ST-elevation myocardial infarction were enrolled. All patients underwent cardiac magnetic resonance (CMR) within 8 days after reperfusion therapy to detect the percentage of necrotic myocardium and the presence of microvascular obstruction or intra myocardial hemorrhage. Echocardiography examination for the first time was performed on the same day as CMR. Segmental and global circumferential strain (CS), radial strain, and longitudinal strain were measured by 2D-STE. Echocardiography was performed again after an average follow-up of 14 months. Results • The segments with functional recovery were associated with higher absolute values of strain parameters at baseline compared to those without functional recovery. The receiver operating characteristic (ROC) curve analysis showed that the sensitivity and specificity of CS≤-7.77% to predict the functional recovery of myocardial segment were 77.17% and 61.40%, respectively (AUC=0.74, P=0.000). Multiple Logistic regression showed that the percentage of necrotic myocardium and global CS (GCS) were the powerful predictors of LV remodeling (P<0.05). According to ROC curve analysis, GCS≥-17.48% had sensitivity of 88.33% and specificity of 69.23%(AUC=0.80, P=0.000) in predicting LV remodeling. Conclusion • Among the strain parameters of 2D-STE, CS may be an ideal predictor of segment functional recovery and LV remodeling after myocardial infarction.
10. Effects of bone marrow mesenchymal cells from immune thrombocytopenia patients on the biological behaviors of megakaryocytes
Journal of Shanghai Jiaotong University(Medical Science) 2018;38(6):616-623
Objective • To investigate changes of immune thrombocytopenia (ITP) patients-derived bone marrow mesenchymal cells (BMCs) in cells survival, cytokines expression as well as the effects of BMCs on the biological behaviors of megakaryocytes. Methods • BMCs were collected from 7 ITP patients and 5 normal controls (NC), and cultivated by the whole marrow adherent method. Surface markers and basal apoptosis rate of BMCs were analyzed by flow cytometry (FCM). Proliferation of BMCs was assessed by CCK-8 method. Phorbol 12-myristate 13-acetate (PMA) was used to stimulate differentiation of HEL cells. The induced HEL cells (inHEL) were divided into 3 groups: inHEL cultured alone (group a), inHEL co-cultured with BMCs derived from ITP patients (group b), inHEL co-cultured with BMCs derived from NC (group c). After 72 h incubation, the expression of cell surface proteins (CD41a, CD42b) and cell apoptosis rate were analyzed by FCM. The mRNA and proteins expression levels of cytokines IL6, IL11, TPO, SCF were detected by real-time fluorescent quantitative PCR (RT-qPCR) and enzyme linked immunosorbent assay (ELISA), respectively. Results • Compared with NC, BMCs from ITP patients grew progressively slowly (Day 4, P=0.039; Day 6, 10, P=0.009; Day 8, P=0.007), cell basal apoptosis rates were increased [AV+PI- (early apoptosis rate), P=0.036; AV+PI+ (late apoptosis rate), P=0.003; AV+PI-/+ (total apoptosis rate), P=0.004]. Compared with group a, the expression of CD41a in group c was much higher (P=0.000). The expression of CD41a in group b was higher than that in group a (P=0.015), but still much less than that in group c (P=0.000). Compared with group a, the early and total apoptosis rate in group b, c and the late apoptosis rate in group c were decreased obviously (all P=0.000), whereas there was no obvious change of the late apoptosis rate in group b. However, compared with group c, the late and total apoptosis rate in group b were significantly increased (both P=0.000). The expression levels of IL6, SCF mRNA and IL6 protein were significantly decreased in ITP BMCs (all P=0.000), but there was no obvious difference in the expression levels of IL11 and TPO between ITP BMCs and NC BMCs. Conclusion • BMCs from ITP patients show some defects in supporting megakaryocytic differentiation and survival under co-culture conditions, which mechanisms are related to the reduction of IL6 and SCF expression.