BACKGROUNDCD44v6 plays an important role in invasion and metastasis of tumor, Livin has anti-apoptotic effects. The present study aimed to explore the expression and clinical significance of CD44v6 and Livin in gastric cancer tissue.

METHODSStreptavidin-peroxidase linked immunohistochemical method was used to determine the expression of CD44v6 and Livin in gastric cancer tissue and adjacent normal gastric tissues from 59 patients with histopathologically confirmed gastric cancer, and in gastric tissue specimens of 15 patients with gastric polyps, and 15 patients with chronic non-atrophic gastritis. The chi-square test was used for comparison of the relevant factors, Spearman's rank correlation test was applied for relationship among positive expression of the proteins.

RESULTSThe expresion of CD44v6 was positive in 64.4% of the gastric cancer patients; 5.1%, 0 and 13.3% in specimens of normal tissues adjacent to the cancer tissues, in gastric tissue specimens of patients with gastric polyps, and patients with chronic non-atrophic gastritis, respectively. The expression of Livin was positive in 52.5% of the gastric cancer tissues, 6.8%, 0 and 6.7% in the adjacent normal gastric tissue, specimens of patients with gastric polyps and chronic non-atrophic gastritis, respectively. The expression of CD44v6 was significantly correlated with the depth of invasion, the degree of differentiation, and lymphnode metastasis of gastric cancer (P < 0.05). The positive expression rate of Livin protein was also significantly correlated with degree of differentiation of gastric cancer cells and metastasis to lymphnodes (P < 0.05), but not correlated with the depth of invasion and pathological types (P > 0.05). The expression of CD44v6 and Livin in the gastric cancer tissue was positively correlated (r(s) = 0.286, P = 0.028).

CONCLUSIONSThe increased expression of CD44v6 and Livin in gastric cancer tissue may be closely related with development and progression of gastric cancer. CD44v6 and Livin may be new biological markers of gastric cancer.

Adaptor Proteins, Signal Transducing ; analysis ; physiology ; Aged ; Female ; Humans ; Hyaluronan Receptors ; analysis ; physiology ; Immunohistochemistry ; Inhibitor of Apoptosis Proteins ; analysis ; physiology ; Male ; Middle Aged ; Neoplasm Proteins ; analysis ; physiology ; Stomach Neoplasms ; chemistry ; metabolism ; pathology

Objective:To investigate the analgesic effect of neurotropin (NTP) on bone cancer pain (BCP) and its preliminary mechanisms in rats.Methods:(1) According to the random number table method, 72 Sprague-Dawley (SD) female rats were randomly and equally divided into 6 groups: normal control group, sham-operated group, BCP model group, BCP+low-dose NTP group, BCP+medium-dose NTP group, and BCP+high-dose NTP group ( n=12). The SHZ-88 breast cancer cells were inoculated into the tibias of rats in the latter 4 groups to establish BCP models. After 15-21 d of modeling, the rats of the latter 3 groups were intraperitoneally administered with 1.2, 2.4 and 3.6 unit NTP, respectively, once per d for 7 consecutive d. The mechanical withdrawal threshold (MWT) changes were measured in each group before BCP and 5, 7, 10, 14, 17, and 21 d after BCP. The number of 5-hydroxytryptamine 7 (5-HT7) positive cells and 5-HT7 protein expression in the ventrolateral periaqueductal gray (vlPAG) were detected by immunohistochemistry and Western blotting, respectively. (2) Twenty-four rats 21 d after BCP modeling were randomly divided into BCP group, BCP+high-dose NTP group (BCP rats with intraperitoneal injection of 3.6 unit NTP), BCP+NTP+SB-269970 group (BCP rats with pretreatment of specific 5-HT7 receptor antagonist SB-269970 in the vlPAG for 30 min, and then, with intraperitoneal injection of 3.6 unit NTP, n=8). The MWT changes were measured in each group before NTP and 15, 30, 45, 60 min after NTP. Results:(1) Seventeen and 21 d after modeling, the MWT values of the modeled hind limb of rats in BCP+low-dose NTP group, BCP+medium-dose NTP group, and BCP+high-dose NTP group were significantly higher than those in BCP group; those in the BCP+high-dose NTP group were significantly higher than those in BCP+low-dose NTP group and BCP+medium-dose NTP group; those in BCP+medium-dose NTP group were statistically higher than those in the BCP+low-dose NTP group ( P<0.05). Twenty-one d after modeling, the number of 5-HT7 receptor positive cells and protein expression in the vlPAG of rats in the BCP+low-dose NTP group, BCP+medium-dose NTP group, and BCP+high-dose NTP group were significantly larger/higher than those in BCP group; those in the BCP+high-dose NTP group were significantly larger/higher than those in BCP+low-dose NTP group and BCP+medium-dose NTP group; those in BCP+medium-dose NTP group were statistically larger/higher than those in the BCP+low-dose NTP group ( P<0.05). (2) At 15, 30, 45 and 60 min after injection of NTP, the MWT values of the modeled hind limb of rats in the BCP+high-dose NTP group and BCP+NTP+SB-269970 group increased gradually, enjoying statistical significance as compared with those in the BCP group at the same time point ( P<0.05); however, the MWT values of the BCP+NTP+SB-269970 group were significantly lower as compared with those in the BCP+high-dose NTP group at the same time point ( P<0.05). Conclusion:The activation of 5-HT7 receptor in the vlPAG is involved in the analgesic effect of NTP on BCP in rats.

BACKGROUND: Chinese medicine is effective for preventing and treating glucocorticoid-induced osteoporosis, however, the underlying mechanism remains unclear. DKK1, an inhibitor of Wnt/β-catenin signaling pathway, can be up-regulated by glucocorticoid. Thereafter, DKK1 is an important target in the prevention and treatment of osteoporosis. OBJECTIVE: To explore the regulatory effect of Zuogui pill on DKK1 in the prevention and treatment of glucocorticoid-induced osteoporosis. METHODS: Eighteen three-month-old female Sprague-Dawley rats were randomly divided into three groups: control group, model group and Zuogui pill group. Rats in the model and Zuogui pill groups received the subcutaneous injection of dexamethasone to establish the model of glucocorticoid-induced osteoporosis. The Zuogui pill group rats were administrated Zuogui pill extracts, and the control rats were given the same volume of normal saline. At 1 month after modeling, the lumbar vertebrae were removed to test the bone mass and microstructures by micro-CT scanning. The biomechanical properties were detected by compression test. The mRNA expression levels of DKK1, Runx2 and CTSK were determined by Qpcr. The serum alkaline phosphatase activity was tested. RESULTS AND CONCLUSION: Compared with the control group, in the model group, the volumetric bone mineral density, trabecular bone volume fraction, trabecular number, and trabecular thickness were significantly decreased (P ＜ 0.05), the trabecular separation and structure model index were significantly increased (P ＜ 0.05). The serum alkaline phosphatase activity was on a decline. The mRNA expression level of DKK1 showed a significant up-regulation (P ＜ 0.05). The mRNA expression level of Runx2 showed a down-regulated trend while mRNA expression level of CTSK showed an up-regulated trend. Compared with the model group, the Zuogui pill group showed significantly enhanced volumetric bone mineral density, trabecular bone volume fraction, and trabecular number (P ＜ 0.05); the structure model index was significantly decreased (P ＜ 0.05); the trabecular separation was reduced; the serum alkaline phosphatase activity was enhanced; the mRNA expression level of DKK1 showed a significant down-regulation (P ＜ 0.05); the mRNA expression level of Runx2 showed an up-regulated trend while mRNA expression level of CTSK showed a down-regulated trend. The vertebral compressive strength in the Zuogui pill group was significantly higher than that in the model group (P＜0.05). In summary, Zuogui pill prevents and treats glucocorticoid-induced osteoporosis possibly through the down-regulation of mRNA expression of DKK1.

BACKGROUNDAttention-deficit hyperactivity disorder (ADHD) is the most common mental and behavioral disorder in school-aged children. This study evaluated the effect of osmotic-release oral system (OROS) methylphenidate (MPH) on cognitive function and academic performance of Chinese school-aged children with ADHD.

METHODSThis 12-week, prospective, multicenter, open-label, self-controlled study enrolled 153 Chinese school-aged children with ADHD and 41 non-ADHD children. Children with ADHD were treated with once-daily OROS-MPH (18 mg, 36 mg, or 54 mg). The primary endpoints were Inattention/Overactivity (I/O) with Aggression Conners Behavior Rating Scale (IOWA) and Digit Span Test at week 12 compared with baseline. Secondary endpoints included opposition/defiant (O/D) subscale of IOWA, Clinical Global Impression (CGI), Coding Test, Stroop Color-word Test, Wisconsin Card Sorting Test (WCST), academic performance on teacher-rated school examinations, and safety at week 12 compared with baseline. Both non-ADHD and ADHD children received the same frequency of cognitive operational test to avoid the possible bias caused by training.

RESULTSA total of 128 patients were evaluated with cognitive assessments. The OROS-MPH treatment significantly improved IOWA Conners I/O subscale scores at week 12 (3.8 ± 2.3) versus baseline (10.0 ± 2.4; P < 0.0001). Digit Span Test scores improved significantly (P < 0.0001) with a high remission rate (81.1%) at week 12 versus baseline. A significant (P < 0.0001) improvement was observed in O/D subscale of IOWA, CGI, Coding Test, Stroop Color-word Test, WCST, and academic performance at week 12 versus baseline. Very few practice-related improvements were noticed in the non-ADHD group at week 12 compared with baseline. No serious adverse events and deaths were reported during the study.

CONCLUSIONSThe OROS-MPH treatment effectively controlled symptoms of ADHD and significantly improved academic performance and cognitive function of Chinese school-aged children with ADHD. The treatment was found to be safe and generally well-tolerated over 12 weeks.

TRIAL REGISTRATIONClinicalTrials.gov, NCT01933880; http://clinicaltrials.gov/ct2/show/NCT01933880?term=CONCERTAATT4099&rank=1.

Administration, Oral ; Attention Deficit Disorder with Hyperactivity ; drug therapy ; physiopathology ; Child ; Cognition ; drug effects ; Female ; Humans ; Male ; Methylphenidate ; administration & dosage ; adverse effects ; therapeutic use ; Neuropsychological Tests ; Prospective Studies ; Treatment Outcome

BACKGROUND AND OBJECTIVEThe most effective therapy against renal cell carcinoma (RCC) is surgical treatment; however, there have been few large-scale studies that focused on the oncological outcome of this disease in China. The aim of the current study was to report the clinicopathological results and cancer-specific survival (CSS) rate in RCC patients after surgical treatment in our center.

METHODSWe retrospectively analyzed the clinicopathological data of 336 RCC patients who underwent radical or partial nephrectomy between 1999 and 2006. Of the 336 patients, 226 were male and 110 were female; the median age was 51 years. Univariate and multivariate analyses were conducted to identify the independent prognostic predictors for this cohort of RCC patients.

RESULTSDuring follow-up, the overall 5-year CSS rate was 81.4%. The 5-year CSS rates for patients with stage-I, -II, -III, and -IV RCC were 94.7%, 88.9%, 68.8%, and 19.3%, respectively. The patients with T1N0M0 (T1) and T2N0M0 (T2) tumors had similar survival curves. For patients with T1 category tumor, the survival rate did not differ significantly between the radical nephrectomy and nephron-sparing surgery groups. For the 21 patients with metastasis confined to the local lymph nodes, the 5-year survival rate was 31.6% after radical nephrectomy and lymph node dissection. For the 15 patients with vena caval tumor thrombus, the 5-year survival rate was 52.5% after radical nephrectomy and tumor thrombus extirpation. Multivariate Cox regression showed that stage was an independent predictor for CSS (hazard ratio, 3.359; P < 0.001).

CONCLUSIONSFor localized RCC, the oncological outcome of this cohort is comparable to that reported in the Western literature. For some patients with locally advanced RCC, aggressive surgical treatment can lead to better long-term survival. However, the prognosis of the patients with metastasis still needs to be improved.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Renal Cell ; pathology ; surgery ; Child ; Child, Preschool ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Kidney Neoplasms ; pathology ; surgery ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Neoplastic Cells, Circulating ; Nephrectomy ; methods ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; Young Adult

OBJECTIVETo investigate the safety and effect of nephron-sparing surgery (NSS) in treatment of T1a and T1b renal cell carcinoma.

METHODSRetrospective analyzed the clinical data of 101 patients with T1 renal cell carcinoma underwent NSS from November 1999 to December 2009.Including 79 male and 22 female with the mean age of 52.3 years (ranged 28 to 79 years). Based on tumor pathologic diameter, 101 patients were divided into T1a group with 62 patient and T1b group with 39 cases. Demographic, intraoperative, postoperative and follow-up data were compared between the 2 groups.

RESULTSThe operation were performed successfully in all the 101 cases. The mean operation time was (151 ± 80) min in group T1a and (158 ± 50) min in group T1b with no statistical difference (P = 0.32). The mean blood loss was (322 ± 596) ml in group T1a and (308 ± 239) ml in group T1b (P = 0.45). Postoperative follow-up ranged from 8 to 102 months with a mean of 38.4 months. One patient in T1b group died of distant metastasis 36 months after operation. Others were no tumor recurred.

CONCLUSIONNephron-sparing surgery is safe and effective for the treatment of T1a and T1b renal cell carcinoma.

Adult ; Aged ; Carcinoma, Renal Cell ; surgery ; Female ; Follow-Up Studies ; Humans ; Kidney Neoplasms ; surgery ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo study the immunomodulatory effects and mechanisms of mesenchymal stem cells (MSC) derived from the bone marrow in acute leukemia patients in vitro.

METHODSBone marrow mononuclear cells from acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) were obtained and cultured in low serum medium. The immunophenotypes were assessed by FACS and immunol histochemistry. The levels of cytokines were evaluated by enzyme linked immunosorbant assay (ELISA). T-cell suppression ability was evaluated by Transwell chamber assay. Moreover, the immunoregulatory ability of AML- and ALL-derived MSC was detected by mixed lymphocyte culture assay.

RESULTSALL-derived MSC showed a typical fibroblast-like morphology. They were positive for CD29, CD44 and CD105, the positive rate were 98.81%, 99.25% and 90.52%, respectively, while negative for CD31, CD45 and CD34. Moreover, ALL- and AML-derived MSC didn't express HLA-DR and co-stirnulatory molecules (CD40, CD80 and CD86). ALL and AML derived MSC could secret several cytokines, such as TGF-β1 (567.58 ± 52.64 and 357.15 ± 33.52), HGF (647.27 ± 102.54 and 219.67 ± 62.37), IL-6 (59.67 ± 15.69 and 54.35 ± 12.31) and IL-11 (102.58 ± 23.54 and 78.21 ± 9.67), the level of secretion of TGF-β1 and HGF were higher in ALL bone marrow derived MSC than that of in AML bone marrow derived MSC. ALL and AML derived MSC significantly suppressed T lymphocyte proliferation in a dose-dependent manner, the counts per minute (CPM) were (3.58 ± 0.54) × 10(4), (2.87 ± 0.33) × 10(4), (1.78 ± 0.51) × 10(4) and (1.15 ± 0.15) × 10(4) for AML derived MSC, and CPM were (1.96 ± 0.31) × 10(4), (1.57 ± 0.28) × 10(4), (0.91 ± 0.41) × 10(4) and (0.22 ± 0.11) × 10(4) for ALL derived MSC when MSC were 0.5 × 10(4), 1 × 10(4), 2 × 10(4) and 5 × 10(4). In addition, the CPM was (4.01 ± 0.72) × 10(4) in control group. The immunosuppressive ability was different between MSCs derived from AML and ALL. The immunosuppressive effect of ALL derived MSC could be reversed by anti-TGF-β1 and anti-HGF antibody.

CONCLUSIONALL-derived MSC show immunoregulatory effect in vitro and this effect is achieved through cytokines. But MSCs derived from AML display abnormal changes in T-cell suppression ability.

Bone Marrow ; immunology ; Bone Marrow Cells ; cytology ; Cell Proliferation ; drug effects ; Cytokines ; pharmacology ; Humans ; Immunophenotyping ; Interleukin-11 ; metabolism ; Interleukin-6 ; metabolism ; Leukemia, Myeloid, Acute ; immunology ; Mesenchymal Stromal Cells ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; immunology ; Transforming Growth Factor beta1 ; metabolism

Adolescent ; Child ; Child, Preschool ; Female ; Hematopoiesis ; Humans ; Infant ; Leukocyte Count ; Male ; Neoplasms ; blood ; mortality ; surgery ; Peripheral Blood Stem Cell Transplantation ; Transplantation, Autologous

OBJECTIVETo observe the effect of recombinant human erythropoietin (rhuEPO) on p-Akt and caspase-9 expressions in the hippocampus of rats with status epilepticus (SE) and explore the neuroprotective mechanism of rhuEPO.

METHODSAdult male SD rats were randomized into control, PTZ, rHuEPO, LY294002 group, and DMSO groups and treated with normal saline (NS), PTZ, PTZ+rHuEPO, PTZ+LY294002+rHuEPO, and PTZ+DMSO+rHuEPO, respectively. The behavioral and electroencephalogram (EEG) changes of the rats were recorded, and the expressions of p-Akt and caspase-9 were detected using immunohistochemistry. The hippocampal expression of caspase-9 mRNA was detected using RT-PCR, and the expressions of Akt and p-Akt proteins were determined with Western blotting.

RESULTSThe p-Akt-positive cell and p-Akt protein expression increased significantly while the caspase-9-positive cell and caspase-9 mRNA expression decreased in rHuEPO group as compared with those in PTZ group (P<0.05). LY294002 treatment prior to rHuEPO injection significantly abolished the effects of rHuEPO on caspase-9 and p-Akt immunohistochemical positivity and caspase-9 mRNA and p-Akt protein expressions (P<0.05).

CONCLUSIONAdministration of rHuEPO activates the PI3K/Akt signaling pathway in SE rats and increases the expression of p-Akt protein to regulate the expression of caspase-9, a regulatory factor of the mitochondrial-dependent apoptotic pathway, and therefore provides anti-apoptotic and neuroprotective effects.

Animals ; Caspase 9 ; genetics ; metabolism ; Erythropoietin ; therapeutic use ; Hippocampus ; metabolism ; Male ; Neuroprotective Agents ; therapeutic use ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; Status Epilepticus ; drug therapy ; metabolism

OBJECTIVETo evaluate the gene-chip detecting rifaman-resistance Mycobacterium tuberculosis applied in TB diagnosis and drug-resistant detection.

METHODSMycobacterium tuberculosis and rifaman-resistant strains among 35 rifaman-resistance isolated strains and 102 sputa specimens from TB patients, 27 sputa specimens from other patients were examined the gene-chips. Results obtained were compared with sputum examination, bacteriological culture and standard drug susceptibility test of Mycobacterium tuberculosis.

RESULTSThirty-five rifaman-resistance strains were detected by gene-chips and 33 were identified as rifaman-resistance strains and the concordance with the traditional drug susceptibility test of Mycobacterium tuberculosis was 94.29%. Twenty-seven sputa specimens from other patients were examined Mycobacterium tuberculosis by the gene-chips, 2 were positive, the detection specialty was 92.59%. Using three methods detecting Mycobacterium tuberculosis among 102 sputa specimens the positive rate respectively was, sputum examination 35.29% (36/102), bacteriological culture 28.43% (29/102), gene-chip 77.45% (79/102). Among 102 sputa specimens only 29 examined Mycobacterium tuberculosis by the traditional drug susceptibility test and 8 were rifaman-resistant strains. While using gene-chip, there were 20 among 102 sputa specimens identified as rifaman-resistance strains. Among total 55 rifaman-resistance strains detected by the gene-chips, the most frequent mutations were those associated with codon 531 (23 of 55; 41.8%), 526 (15 of 55; 27.27%) and 516 (9 of 55; 16.36%).

CONCLUSIONResults showed that this was a rapid, simple and highly specific method when using gene-chip to detect Mycobacterium tuberculosis and rifaman-resistant strains.

China ; epidemiology ; DNA, Bacterial ; genetics ; Drug Resistance, Bacterial ; genetics ; Female ; Humans ; Male ; Mycobacterium tuberculosis ; drug effects ; genetics ; isolation & purification ; Oligonucleotide Array Sequence Analysis ; Oligonucleotide Probes ; Point Mutation ; Rifampin ; pharmacology ; Sensitivity and Specificity ; Sputum ; microbiology ; Tuberculosis, Multidrug-Resistant ; epidemiology ; microbiology ; Tuberculosis, Pulmonary ; epidemiology ; microbiology