BACKGROUNDTat-interacting protein 30 (TIP30) has been reported to be a tumor suppressor, with reduced or absent expression in various tumors. However, its role in bladder urothelial cancer (BUC) has not been investigated. Therefore, herein, we investigated the expression of TIP30 protein in BUC and normal bladder mucosa and the clinical significance of TIP30 expression in the prognosis of BUC.

METHODSWe reviewed data from 79 cases of BUC and 15 adjacent tissue samples from 79 patients treated at our institution between 2004 and 2007. TIP30 expression was examined by immunohistochemistry. The relationship between TIP30 expression and tumor stage, histological grade, and survival was analyzed. Differences between groups were evaluated using the t-test or matched-pairs test, and differences in the survival rates were analyzed with the log-rank test.

RESULTSTIP30 protein expression was significantly reduced in BUC tissue (t = -6.91, P < 0.05) compared with normal tissue samples, and in invasive bladder cancer (t = 10.89, P < 0.05) compared with superficial bladder cancer. TIP30 protein expression differed significantly among different differentiated groups classified either according to the World Health Organization (2004, F = 17.48, P < 0.01) or World Health Organization (1973, F = 10.68, P < 0.01). TIP30 protein expression was significantly reduced in high-grade papillary urothelial carcinoma compared with papillary urothelial neoplasm of low malignant potential (P < 0.05) and low-grade papillary urothelial carcinoma (P < 0.05). Meanwhile, TIP30 protein expression was significantly reduced in Grade III BUC, compared with Grade I (P < 0.05) and Grade II (P < 0.05). Patients with low TIP30 expression showed a higher incidence of disease progression than those with high TIP30 expression (t = 2.63, P < 0.05). Kaplan-Meier survival analysis showed a strong positive relationship between TIP30 expression and overall survival (OS) (χ2 = 17.29, P < 0.05).

CONCLUSIONSTIP30 expression was associated with clinical tumor stage in BUC, suggesting that it might play an important role in disease progression. Furthermore, TIP30 might predict postoperative OS. Thus, its evaluation might be useful for predicting prognosis.

BACKGROUNDDiabetic nephropathy (DN) is the most common and serious microvascular complication of diabetes. To date, the gold standard for identifying DN and nondiabetic renal disease (NDRD) is a renal biopsy; however, there is currently no reliable diagnostic marker to identify DN and NDRD in a noninvasive manner. This study aimed to investigate the different glycopatterns in urine specimens of DN patients and NDRD patients for a differential diagnosis.

METHODSIn total, 19 DN patients and 18 NDRD patients who underwent renal biopsies between March 2015 and March 2016 at the Chinese People's Liberation Army General Hospital were enrolled in this study. A lectin microarray was used to investigate the glycopatterns in the urinary protein of the 37 patients. Ratio analysis and one-way analysis of variance were used to screen altered glycopatterns. Then, the altered glycopatterns between the DN and NDRD groups were verified by a urinary protein microarray among another 32 patients (15 with DN and 17 with NDRD), and receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of the altered glycopatterns in differentiating DN and NDRD. Finally, lectin blotting was used to evaluate the altered glycosylation in protein level.

RESULTSThe result of lectin microarrays revealed that the relative abundance of the (β-1,4)-linked N-acetyl-D-glucosamine (GlcNAc) recognized by lectin Datura stramonium agglutinin (DSA) was significantly higher in urinary protein in DN patients than that in NDRD patients (fold change >1.50, P < 0.001). Subsequently, the results of urinary protein microarrays were consistent with lectin microarrays (P < 0.05). Furthermore, the ROC curve showed that glycopatterns could effectively distinguish DN from NDRD patients (area under the ROC curve = 0.94, P < 0.001). DSA lectin blotting showed that glycoproteins, with a molecular weight of approximately 50,000, demonstrated a difference in urine samples between DN patients and NDRD patients.

CONCLUSIONSThe relative abundance of (β-1,4)-linked GlcNAc recognized by lectin DSA and urinary glycoprotein with a molecular weight of approximately 50,000 are significantly different between DN and NDRD patients, indicating that the glycopatterns could be used as potential biomarkers for a differential diagnosis.

OBJECTIVETo study the clinical outcome of manipulation release combined with arthroscopic debridement and synovia resection under general anesthesia for early hip involvment in patients with ankylosing spondylitis.

METHODSManipulation release combined with arthroscpic debridement and synovium resection were performed for hip lesion in 22 patients with ankylosing spondylitis from June 2011 to June 2013, incuding 6 males and 16 females with anverage age of 24.7 years ranging from 17 to 23 years. The course of the diseases was from 10 to 41 months(22.1 months on average). After 6 months of conservative treatment, hip pain and other symptoms were no relief. The preoperative and postoperative follow-up evaluation was performed and compared by the hip movement, VAS pain score, mHHS score and NAHS score.

RESULTSAll the patients were followed up for 26 to 44 months with an average of 30.2 months. The range of motion in active flexion-extension, abduction-adduction, internal-external rotation in 0° flexion and 90° flexion increased from (78.2±10.2)°, (36.3±6.4)°, (31.1±9.2)° and (37.3±10.5)° before operation to (113.5±8.4)°, (55.7±8.4)°, (58.7±2.1)° and (60.1±9.8)° after operation, respectively. The VAS scores decreased from 8.5±9.4 before operation to 5.5±7.1 after operation. The modified Harris and NAHS scores increased from 60.8±6.9 and 56.9±6.25 before operation to 88.1±10.4 and 84.6±5.4 after operation, respectively.

CONCLUSIONSManipulation release combined with arthroscopic debridement and synovium resection under general anesthesia could effectively control the progression of hip lesion in patients with ankylosing spondylitis restoring the ROM, relieve pain symptoms, delay joint deformity and ankylosis with less bleeding, faster recovery, and significantly improve patients' quality of life.

The experiment was aimed to investigate the difference of plasma concentration and pharmacokinetic parameters between liposome and aqueous solution of toatal ginsenoside of ginseng stems and leaves in rats, such as ginsenosides Rg₁, Re, Rf, Rb₁, Rg₂, Rc, Rb₂, Rb₃, Rd. After intravenous injection of liposome and aqueous solution in rats, the blood was taken from the femoral vein to detect the plasma concentration of the above 9 ginsenoside monomers in different time points by using HPLC. The concentration-time curve was obtained and 3p97 pharmacokinetic software was used to get the pharmacokinetic parameters. After the intravenous injection of ginsenosides to rats, nine ginsenosides were detected in plasma. In general, among these ginsenosides, the peak time of the aqueous solution was between 0.05 to 0.083 3 h, and the serum concentration peak of liposome usually appeared after 0.5 h. After software fitting, the aqueous solution of ginsenoside monomers Rg₁, Re, Rf, Rg₂, Rc, Rd, Rb₃ was two-compartment model, and the liposomes were one-compartment model; aqueous solution and liposome of ginsenoside monomers Rb₁ were three-compartment model; aqueous solution of ginsenoside monomers Rb₂ was three-compartment model, and its liposome was one-compartment model. Area under the drug time curve (AUC) of these 9 kinds of saponin liposomes was larger than that of aqueous solution, and the retention time of the liposomes was longer than that of the aqueous solution; the removal rate was slower than that of the aqueous solution, and the half-life was longer than that of the water solution. The results from the experiment showed that by intravenous administration, the pharmacokinetic parameters of two formulations were significantly different from each other; the liposomes could not only remain the drug for a longer time in vivo, but also reduce the elimination rate and increase the treatment efficacy. As compared with the traditional dosage forms, the total ginsenoside of ginseng stems and leaves can improve the sustained release of the drug, which is of great significance for the research and development of new dosage forms of ginsenosides in the future.

OBJECTIVETo evaluate the safety and efficacy of submucosal tunneling endoscopic septum division (STESD) for escophageal diverticulum.

METHODSClinical data of six consecutive patients with symptomatic esophageal diverticula who received STESD in Endoscopy Center of Zhongshan Hospital, Fudan University from April 2016 to November 2016 were analyzed retrospectively. STESD was performed as following: mucosal entry was made 3 cm from the septum of esophageal diverticulum; submucosal tunnel was created towards the septum; after the satisfactory exposure of the septum, endoscopic division was made down to the bottom of the diverticulum; mucosal closure of the tunnel entry was made. The symptoms were scored using a system modified according to Eckardt score, namely dysphagia, heartburn, regurgitation, weight loss and retrosternal pain with each ranging from 0 to 3 (maximum score 15, minimum score 0, the higher the score, the more severe the symptoms).

RESULTSThere were four males and two females with median age of 56.5 (range 50-67) years. Four patients were epiphrenic diverticula, and the other two were Zenker's diverticula. Median duration of disease was 2.5 years (range 5 months-29 years). No previous treatment was attempted. All the patients completed STESD successfully. The median septum division length was 2.5(1-4) cm. The median number of metallic clips for mucosal closure was 5(2-6). The median operation time was 51.5 (33-135) min. No major adverse events, such as perforation or bleeding were found in perioperative period. The median time of hospital stay was 5(3-9) days. All the patients had symptom relief after operation. One patient with Zenker's diverticulum reported foreign body sensation after operation and experienced relief two weeks afterwards. During a median follow-up time of 5(4-10) months, the median symptom score of 6 cases was 4.5 (1-13) before and 0.5 (0-4) after operation. The symptom scores went down to zero in 3 patients (preoperative scores 13, 1, 1, respectively), and down to 1 in 2 patients with main symptom of backflow (preoperative scores 5, 4, respectively). One patient with 29 years history of disease did not report obvious improvement in symptoms (preoperative and postoperative scores 5, 4, respectively).

CONCLUSIONSubmucosal tunneling endoscopic septum division is efficient and safe to relieve symptomatic esophageal diverticulum in short term.

Aged ; Diverticulum, Esophageal ; surgery ; Endoscopy, Digestive System ; methods ; Female ; Humans ; Length of Stay ; Male ; Middle Aged ; Mucous Membrane ; Operative Time ; Perioperative Period ; Retrospective Studies ; Surgical Instruments ; Treatment Outcome ; Video-Assisted Surgery ; methods ; Zenker Diverticulum ; surgery

OBJECTIVETo investigate the clinical features and surgical strategy for pediatric intractable epilepsy due to posterior quadrantic cortical dysplasia and to assess the surgical outcomes.

METHODSThe clinical features and preoperative evaluation results of 14 children with intractable epilepsy due to posterior quadrantic cortical dysplasia were retrospectively analyzed. The localization values of video-electroencephalography and intraoperative monitoring and the indications, advantages and disadvantages of temporoparietooccipital disconnection were evaluated.

RESULTSThe 14 children had different seizure types, of which spasm was the most common one. The lesions of cortical dysplasia involved the central cerebral region in 2 cases. After temporoparietooccipital disconnection in 14 patients, 13 cases were seizure-free; only one case still had seizures, but the frequency dropped by more than 50%.

CONCLUSIONSTemporoparietooccipital disconnection is a safe and effective surgical procedure for children with intractable epilepsy due to posterior quadrantic cortical dysplasia.

Child ; Child, Preschool ; Electroencephalography ; Epilepsy ; etiology ; physiopathology ; surgery ; Evoked Potentials, Somatosensory ; Female ; Humans ; Infant ; Male ; Malformations of Cortical Development ; complications

To reveal the protective and anti-apoptosis effect of compound Ginkgo biloba granules on oxidative stress injury of human umbilical vein endothelial cells (HUVEC). Negative control group, H2O2 model group and 4 drug pretreatment groups (80, 160, 320, 640 mg• L⁻¹) were established. The cell proliferation, morphological changes in each group after oxidative stress injury was detected by MTT assay and through microscope observation respectively. The content of LDH, MDA, SOD and NO and SOD activity in supernatant were detected to judge the protection effect of the drugs on endothelial cells. The protective effect on HUVEC apoptosis was analyzed by Caspase-3 activity test and Annexin V-FITC/PI staining. Western blot was used to observe the expression of apoptosis-related proteins Bcl-2 and Bax. Results showed that 1 200 μmol• L⁻¹ H2O2 can induce oxidative stress injury in endothelial cells and reduce the cell survival rate; cell proliferation inhibition degree is positively correlated with the effect time of H2O2. Besides, 80, 160, 320 640 mg•L⁻¹ compound Ginkgo biloba granules can protect HUVEC from oxidative stress injury, recover the normal proliferation level of cells, improve their state, prohibit cell apoptosis, and can up-regulate and down-regulate the expression level of Bcl-2 and Bax respectively. In conclusion, compound G. biloba granules can protect HUVEC from the oxidative stress injury induced by H2O2, its mechanism may be correlated with inhibition of the mitochondrial apoptotic pathway in HUVEC.

BACKGROUNDCD200 and its receptor CD200R are both type-1 membrane glycoproteins, which are members of the immunoglobulin superfamily (IgSF). Besides the inhibitory effect on macrophages, CD200/CD200R also play an important role in regulating the regulatory T cells, allergicreaction, autoimmune diseases, allograft, neurological diseases and other autoimmune-related diseases, etc.

OBJECTIVETo investigate the role of CD200 and its receptor in the graft versus host disease (GVHD).

METHODSExperimental samples were divided into aGVHD group, non-aGVHD group, cGVHD group and non-cGVHD group, the healthy persons were used as normal controls. Firstly, the expression levels of CD200 and CD200R on CD19+ cell, CD3+ cell and dendritic cell (CD19- CD14- CD1c+) surfaces in each group were detected by using flow cytometry, so as to determine whether there were expression differences among each groups. Then, the mRNA levels of each groups were tested by using real-time quantitative polymerase chain reaction for finding the differences of mRNA expression level among each group. Finally, the peripheral blood mononuclear cells of the patients and healthy controls were co-cultured with anti-CD200R1 antibody for 48 hours, and the interleukin-10 level in the co-culture system was tested by using enzyme linked immunosorbent assay for verifying the function of CD200/CD200R.

RESULTSThe CD200 expression level on CD19+ cell surface in the aGVHD group and non-aGVHD group was both lower than that in healthy control group; that in the non-aGVHD group was higher than that in the aGVHD group. The CD200 expression level on CD19+ CD200+ cells in the non-cGVHD group were higher than that in the cGVHD group and healthy control group. There were no significant differences of CD200 and CD200R expression levels on CD3 cells and dendritic cells among all groups. The CD200 mRNA expression levels in the aGVHD group and cGVHD group were both lower than the healthy control group. The CD200 mRNA expression level was lower in the aGVHD group than in the non-aGVHD group, and was lower in the cGVHD group than in the non-cGVHD group. There was no significant difference of the CD200R mRNA expression level among all groups. After the peripheral blood mononuclear cells of the patients and healthy controls were co-cultured with anti-CD200R1 antibody for 48 hours, the interleukin-10 concentration decreased with the increasing of anti-CD200R1 antibody concentrations in the co-culture system.

CONCLUSIONThe CD200/CD200R may play a role in the pathogenesis of GVHD after allo-HSCT.

Antigens, CD ; metabolism ; Coculture Techniques ; Dendritic Cells ; metabolism ; Flow Cytometry ; Graft vs Host Disease ; metabolism ; Hematopoietic Stem Cell Transplantation ; Humans ; Interleukin-10 ; metabolism ; Leukocytes, Mononuclear ; Membrane Glycoproteins ; metabolism ; RNA, Messenger ; metabolism ; Receptors, Cell Surface ; metabolism ; Transplantation, Homologous

Catharanthus roseus can produce a variety of terpenoid indole alkaloids (TIA), most of which exhibit strong pharmacological activities. Hence, biosynthesis and regulation of TIA have received recent attention. 3α (S)-strictosidine is an important node in TIA biosynthesis, which is a condensation product of secologanin and tryptamine. The former is produced in iridoid pathway, and the latter is produced in indole pathway. Vindoline and catharanthine, which are produced respectively by 3α (S)-strictosidine via multi-step enzymatic reaction, can form α-3, 4-anhydrovinblastine by the condensation reaction. Then, vinblastine and vincristine are generated from α-3, 4-anhydrovinblastine. Many transcription factors are involved in the regulation of TIA synthesis, such as AP2/ERF and WRKY. Illumination of biosynthetic pathway has laid a foundation for the study of synthetic biology. Today, 3α (S)-strictosidine and vindoline have been synthesized in heterologous hosts Saccharomyces cerevisiae.Research about synthetic biology and the regulation mechanisms will provide a guidance for the production and development of TIA drugs in C. roseus.

OBJECTIVETo study the effect of carboxyamidotriazole (CAI) on adjuvant arthritis (AA) in rats.

METHODSThe rats were randomly divided into normal group,two vehicle groups (polyethylene glycol 400 control and normal sodium control group), CAI-treated groups (10, 20, and 40 mg/kg) and positive control dexamethasone group. Freund's completed adjuvant was used to induce AA in rats. The arthritis index (AI) was scored, and X-ray check of the hind limbs and histopathological examination were performed. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in the inflamed paw tissues were measured.

RESULTSThe administration of CAI significantly decreased the AI, restored the body weights, and ameliorated the radiological and histopathological features of joint destruction in AA rats (P<0.05, P<0.01). In addition, CAI reduced the TNF-α, IL-1β, and IL-6 levels in the inflamed paw tissues (P<0.05, P<0.01).

CONCLUSIONCAI has therapeutic effect on AA rats, which may be achieved by decreasing the pro-inflammatory cytokines at the site of inflammation.

Animals ; Arthritis, Experimental ; Freund's Adjuvant ; Interleukin-1beta ; Interleukin-6 ; Rats ; Triazoles ; Tumor Necrosis Factor-alpha